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Longevity

Longevity denotes the span of an organism's life, encompassing both average lifespan within a and exceptional instances of extended survival, with particularly scrutinized in fields like for its interplay with biological aging processes. In humans, average at birth has more than doubled over the past century, rising from approximately 32 years in 1900 to 73.3 years globally in 2024, primarily driven by reductions in early-life mortality from infectious diseases, enhanced public , nutritional improvements, and rather than fundamental alterations to aging itself. The verified maximum human lifespan stands at 122 years and 164 days, recorded by (1875–1997), underscoring a biological ceiling that has not demonstrably shifted despite these gains. Contemporary efforts to extend emphasize —the period of life free from chronic disease—over mere chronological extension, targeting such as , genomic instability, and metabolic dysregulation through interventions like caloric restriction mimetics (e.g., rapamycin, which extends lifespan 9–14% in mid-life mice) and therapies. These approaches yield promising results in animal models but face skepticism in human applications, where peer-reviewed analyses indicate radical (e.g., routine survival beyond 115–125 years) remains improbable this century absent breakthroughs in reversing core aging drivers, amid debates over whether past expectancy gains have plateaued due to persistent age-related pathologies like cancer and . Key controversies include overhyped claims from longevity advocacy groups contrasting with empirical data showing decelerating gains in high-longevity nations since 1990, highlighting the need for rigorous, causal evidence over speculative narratives in funding-biased research landscapes.

Core Concepts

Definitions and Metrics

Longevity refers to the duration of an individual's life span, particularly emphasizing extended survival beyond typical norms, independent of underlying aging processes. In biological contexts, it denotes the capacity to achieve a prolonged , often measured against average age at death for a given or . For humans, verified maximum longevity stands at 122 years, recorded by who died in 1997. Key metrics for assessing longevity include lifespan, defined as the total years an individual lives from birth to death, and maximum lifespan, the longest observed duration within a under optimal conditions. at birth quantifies the average years a newborn is projected to live, assuming current age- and sex-specific mortality rates persist throughout life; globally, this averaged 73.4 years in 2019 per data. Healthy life expectancy (HALE) extends this by estimating years lived in full health, subtracting periods of significant , with a global figure of 63.7 years in 2019. In longevity research, additional metrics evaluate population-level survival patterns, such as percentile longevities (e.g., age at which 10% of a survives) or parameters from the Gompertz-Makeham model, which describes exponential mortality increase with age. These allow comparisons across or interventions, distinguishing intrinsic limits from extrinsic factors like . Biological aging proxies, including epigenetic clocks that predict chronological age via , serve as indirect longevity indicators by estimating "biological age" divergence from calendar age. Such metrics prioritize empirical survival data over subjective health perceptions to maintain objectivity.

Distinctions: Lifespan, Life Expectancy, and Healthspan

Lifespan refers to the total duration of an individual's life from birth to death, with the maximum human lifespan—the longest verified age attained—standing at 122 years and 164 days, as recorded for (1875–1997). In biological research, lifespan encompasses both average longevity within a population and the species-specific upper limit, influenced by genetic, environmental, and factors, though it remains distinct from probabilistic averages. Life expectancy, by contrast, is a demographic statistic representing the average number of years a newborn or person at a specific age can expect to live under prevailing mortality conditions. Calculated via life tables from vital statistics, it aggregates data to forecast , such as the U.S. figure of 78.4 years at birth in 2023, varying by sex, location, and socioeconomic variables. Unlike individual lifespan, life expectancy is inherently a metric, subject to revision with changing rates from , accidents, or interventions, and does not predict any single person's outcome. Healthspan delineates the subset of lifespan spent in robust , free from debilitating conditions, frailty, or , often operationalized through metrics like disability-free years or healthy (HALE). Coined by the National Institute on Aging to underscore quality over mere extension, it highlights the morbidity-free period, with global data revealing a persistent healthspan-lifespan gap of 10–20 years in high-income nations, where late-life erodes vitality despite prolonged survival. Research in emphasizes that decoupling healthspan from lifespan—via delayed onset of age-related decline—offers greater welfare gains than equivalent total-year extensions, as evidenced by compression of morbidity models showing reduced frailty duration in cohorts with improved early-life conditions. These distinctions underpin longevity studies: lifespan sets biological ceilings testable against outliers like supercentenarians; life expectancy tracks epidemiological progress, such as post-1800 gains from and vaccines lifting averages from under 40 to over 70 years globally; while healthspan prioritizes causal interventions targeting drivers, like or telomere attrition, to minimize the years of decline that burden individuals and systems. Over-citation of mainstream metrics without healthspan scrutiny risks overlooking how medical advances, such as aggressive chronic management, may inflate expectancy at the cost of vitality-compressed years, per analyses questioning optimistic projections beyond empirical limits.

Human Longevity Patterns

Historical Increases in Life Expectancy

Prior to the , global at birth averaged around 30-31 years, heavily skewed by high and rates from infectious diseases, , and poor , though adults who survived to age 15 often reached 50-60 years. These estimates derive from demographic reconstructions using historical records, burial data, and skeletal analyses, revealing that maximum human lifespan remained constrained near 70-80 years even in , with gains limited by recurrent epidemics and famines. The marked initial modest increases, particularly in and , as industrialization enabled better and urban sanitation reforms like sewage systems and , reducing deaths from such as ; by 1900, global had edged to about 32 years, still dominated by childhood mortality exceeding 40% in many regions. In leading nations like and , rose from around 40 years in 1800 to 50 by 1900, driven by these interventions rather than medical cures, though global averages lagged due to persistent and in and . The 20th century saw exponential gains, with global surging from 32 years in 1900 to 46 by and 67 by 2000, primarily from conquest of infectious diseases via vaccines (e.g., eradication by 1977, and pertussis reductions post-1920s), antibiotics introduced in the , and widespread access to clean , averting millions of early deaths. plummeted from over 200 per 1,000 births in 1900 to under 50 by globally, accounting for much of the early-century rise, while post-1950 advances included better maternal care and , though these shifted focus to diseases without substantially extending the biological maximum lifespan beyond historical peaks.
PeriodGlobal Life Expectancy at Birth (years)Key Contributors
Pre-1800~30-31Limited; high early-life mortality
190032 beginnings
195046, antibiotics
200067 expansion,
202171Continued chronic disease management
These increases reflect environmental and technological interventions compressing morbidity into later life, rather than aging itself, as evidenced by stable age at death around 70-80 years across eras when excluding early fatalities. Global at birth reached 73.3 years in 2024, reflecting an increase of 8.4 years since 1995, primarily driven by reductions in child and infectious disease mortality in developing regions. However, progress has slowed compared to earlier decades, with the causing a temporary dip of approximately 1.8 years globally between 2019 and 2021 before partial recovery. In high-income countries, gains have stagnated or reversed in recent years due to rising deaths from drug overdoses, obesity-related conditions, cardiovascular diseases, and external causes like suicides and accidents, offsetting advances in and other areas. Regional disparities persist, with leading at over 80 years—such as at 84.8 years and at 84.4 years in 2025 estimates—while lags below 65 years, though showing faster recent improvements from interventions and vaccinations. In the United States, stood at 78.4 years in 2023, trailing comparable nations by about 4 years, with projections indicating only modest gains to 79.4 years by 2025 amid ongoing epidemics of opioids and metabolic disorders. Healthy life expectancy, or healthspan, trails lifespan by roughly 12 years globally, at 61.9 years as of recent data, highlighting increasing years lived with disability from chronic conditions. Projections from the ' 2024 World Population Prospects anticipate global rising to 77.0 years by 2050 under medium-variant assumptions of continued decline and mortality reductions, though at a decelerating rate of about 0.2 years per decade. Alternative forecasts from the Institute for Health Metrics and Evaluation predict gains of 4.9 years for males and 4.2 years for females from 2022 levels by 2050, tempered by risks from , , and aging demographics. These estimates assume no major disruptions like future pandemics or geopolitical conflicts, but evidence from developed nations suggests intrinsic limits to further extensions without breakthroughs in addressing senescence-related diseases, as historical gains from and antibiotics have largely plateaued.

Exceptional Cases: Supercentenarians

A is defined as a who has attained of years or more. Verification of such extreme ages requires rigorous documentation, including birth certificates, records, and baptismal entries, to exclude fraud or errors common in unverified claims from regions with poor historical record-keeping. The (GRG) maintains the primary database of validated cases, emphasizing empirical validation over anecdotal reports. The record for the longest verified human lifespan belongs to Jeanne Louise Calment of , who lived 122 years and 164 days from February 21, 1875, to August 4, 1997. Her age was confirmed through over 30 documents cross-referenced by demographers, including early photographs and family records. Despite a 2018 challenge alleging identity substitution with her daughter, subsequent analyses upheld the original validation based on inconsistent claims and matching physical descriptions across decades. Validated supercentenarians number over 600 historically, with approximately 200-250 living as of 2025, though exact counts fluctuate due to ongoing validations and deaths. The phenomenon remains exceedingly rare, occurring in roughly 1 in 1,000 centenarians, with incidence rising modestly due to improved global healthcare and verification rather than fundamental biological shifts. Demographically, about 90% are , reflecting greater resilience to age-related mortality from cardiovascular and other diseases. Geographically, validated cases cluster in nations with robust civil registries, such as (highest per capita), the , , and , rather than unverified "blue zones" like Okinawa or where claims often fail scrutiny. Extreme longevity in supercentenarians stems primarily from genetic factors that confer resistance to major killers like cancer, , and neurodegeneration, often delaying disease onset until after age 105. Studies of their genomes reveal rare variants in genes regulating , , and , with lower inflammatory biomarkers akin to those in much younger adults. While lifestyle elements like moderate and avoidance of correlate in some cases, heritability estimates exceed 30% for reaching 110, underscoring innate biological limits over modifiable behaviors in outliers. Supercentenarians typically experience compressed morbidity, remaining functionally independent until shortly before death, challenging assumptions of inevitable frailty.

Primary Biological Determinants

Genetic Factors and Heritability

Heritability estimates for human lifespan from twin studies typically range from 20% to 30%, indicating a moderate genetic contribution after accounting for environmental factors. A Danish twin study of 2,872 pairs born between 1870 and 1900 reported heritability of 0.26 for males and 0.23 for females, with genetic dominance variance explaining a portion of the effect. More recent analyses, adjusting for confounders like assortative mating, suggest heritability may reach approximately 50%, doubling prior estimates by isolating additive genetic variance. Family studies reinforce genetic influences, showing siblings of have significantly higher probabilities compared to the general , with increasing at ages. Genome-wide association studies (GWAS) have identified multiple loci associated with longevity, though individual variants explain only small fractions of variance due to its polygenic nature. Key variants include those near APOE, linked to and Alzheimer's risk, and FOXO3, involved in insulin/IGF-1 signaling, with protective alleles enriched in long-lived individuals. Meta-analyses of large cohorts, such as participants, have pinpointed over 20 loci, including CHRNA3/5 related to and LPA for cardiovascular , highlighting pathways like and . In exceptional longevity cases like centenarians and supercentenarians, genetic factors appear more pronounced, with evidence of depleted loss-of-function mutations and increased frequencies of protective variants that mitigate age-related diseases. Studies of centenarians reveal superior genomic stability, including variants in maintenance and IGF-1 pathways, contributing to against common . However, GWAS success remains limited for extreme longevity due to small sample sizes and the need for rare variant detection, underscoring the interplay of many low-effect alleles rather than single high-impact genes. Parental lifespan strongly correlates genetically with offspring longevity, supporting transgenerational estimates around 0.2-0.3 in population data.

Intrinsic Biological Limits

The refers to the finite number of divisions, typically 50 to 70, that normal human cells can undergo before entering replicative , a state of irreversible arrest. This phenomenon, first described in 1961, arises primarily from progressive telomere shortening during , as cannot fully replicate chromosome ends without telomerase activity, which is absent or minimal in most adult cells. prevents further proliferation, leading to tissue dysfunction and contributing to organismal aging.60908-2/fulltext) Telomere attrition correlates with species lifespan, with faster shortening rates observed in shorter-lived mammals, suggesting it imposes an intrinsic constraint on regenerative capacity and overall longevity. In humans, telomeres shorten at an average rate of 20-40 base pairs per year, reaching a critical length that triggers senescence pathways like p53 and p21 activation, limiting tissue repair and homeostasis. While telomerase can elongate telomeres in stem cells and germ lines, its upregulation in somatic cells risks oncogenesis, underscoring a evolutionary trade-off that caps lifespan to minimize cancer risk. Empirical data from centenarians show telomere lengths approaching critically short levels, aligning with observed maximum human ages around 122 years, as verified by Jeanne Calment's documented survival. The Gompertz-Makeham law of mortality mathematically describes an intrinsic biological limit through exponential increases in age-specific death rates after maturity, reflecting accelerating frailty from accumulated molecular damage rather than external hazards alone. This pattern, where mortality doubles roughly every 8 years in humans post-30, implies a finite lifespan ceiling, as survival curves plateau near 115-125 years in demographic models fitted to historical data from high-longevity populations. Longitudinal analyses of physiological markers, such as declining physiological reserve and criticality thresholds, indicate that end-of-life instability emerges as an emergent property of complex biological systems, independent of or medical interventions. Recent projections, accounting for decelerating gains since the 1990s, support a provisional upper bound near 120 years under , though radical interventions could theoretically shift this.

Modifiable Influences

Lifestyle Interventions

Lifestyle interventions encompass modifiable behaviors that influence longevity through empirical associations with reduced mortality risk and extended life expectancy. Observational and interventional studies demonstrate that avoiding tobacco use, engaging in regular physical activity, adhering to nutrient-dense diets, optimizing sleep duration, and moderating caloric intake can collectively add several years to lifespan, with effects varying by age of adoption and adherence duration. Smoking cessation stands out as one of the most impactful interventions, with quitting at any age yielding substantial gains in . Individuals who cease by age 40 avert approximately 90% of the risk attributable to continued use, potentially adding up to 10 years compared to persistent smokers. Even cessation after age 65 can extend life by at least 1 year for about 25% of quitters, with nearly 10% gaining 8 or more years, based on analyses adjusting for comorbidities. These benefits arise from rapid reductions in cardiovascular and cancer risks, though former smokers retain elevated hazards relative to never-smokers. Physical activity consistently correlates with prolonged lifespan across meta-analyses of studies. Regular exercise is linked to gains of 0.4 to 6.9 years, with optimal volumes around 60 minutes weekly of resistance training or 150-300 minutes of moderate aerobic activity reducing all-cause mortality by 15-30%. Higher volumes, up to 2-4 times guideline recommendations, further lower death risk without a clear upper for harm in healthy adults, emphasizing total volume over intensity alone. Mechanisms include improved cardiometabolic function and reduced , though causality is inferred from dose-response patterns rather than randomized trials due to ethical constraints. Dietary patterns prioritizing whole foods, such as those high in fruits, , nuts, and while low in processed meats and sugars, can extend by up to 10 years if adopted in . Modeling studies estimate that shifting from typical diets to optimized ones—reducing and increasing plant-based intake—yields 8-10 year gains at 60, diminishing but still positive (3 years) at 80. derives from large prospective cohorts like the , where sustained adherence correlates with lower incidence, though confounding by socioeconomic factors persists. Caloric restriction (CR) without , typically 10-25% below intake, slows biological aging markers in s, as shown in the CALERIE trial where participants exhibited a 2-3% reduction in aging pace over 2 years. While robust lifespan extension occurs in animal models, data indicate healthspan benefits via metabolic shifts like enhanced and reduced , but long-term adherence challenges limit direct mortality evidence. Optimal of 7-8 hours per night minimizes all-cause mortality risk, with deviations—less than 5 or more than 9 hours—elevating hazard by 10-30% in meta-analyses of prospective studies. Short independently predicts higher cardiovascular events, while regularity may outperform duration alone in forecasting longevity. These associations hold after adjusting for confounders like , underscoring sleep's role in restorative processes. Multidomain adherence amplifies effects; for instance, combining non-smoking, exercise, , and moderate alcohol yields 10-14 year expectancy gains over low-adherence lifestyles in population models. However, interventions must account for individual variability, as genetic factors moderate responses, and overemphasis on isolated behaviors ignores synergistic interactions.

Environmental and Socioeconomic Factors

Higher consistently correlates with longer across populations. In the United States, analysis of tax records from 1988 to 2011 revealed a 14.6-year in at age 40 between the top 1% and bottom 1% earners among men, and a 10.1-year among women. This disparity arises from differential access to healthcare, , and safer living conditions, as well as lower exposure to occupational hazards and associated with . Low contributes approximately 9.7% to 13.4% of the socioeconomic in , often compounded by behavioral risks like . Education and occupation further mediate these effects, with higher levels linked to extended healthy lifespan. A scoping review of working life expectancy found that individuals in lower socioeconomic positions exit the labor market earlier due to health impairments, independent of baseline ill-health controls. Globally, socioeconomic development metrics like GDP per capita positively predict , while —a for early-life socioeconomic conditions—negatively impacts it. In high-income nations like , the income-life expectancy gradient has widened since the , even as overall stabilized, suggesting causal pathways beyond mere income dispersion, such as cumulative advantages in preventive care. Ambient represents a major environmental determinant, reducing global average by 2.2 to 2.9 years, exceeding impacts from or in some models. Fine particulate matter (PM₂.₅) from combustion drives this effect, with estimated at 8.8 million annually worldwide. Regions with high pollution, such as parts of and , face losses up to 5-6 years per person if meeting WHO standards. Other environmental exposures, including water contamination and extreme climates, compound risks; moderate climates correlate with higher longevity than arid or polar extremes due to reduced physiological stress. Urbanization introduces mixed influences, with walkable, mixed-age communities associated with centenarian prevalence in studies from Washington state, likely via enhanced social connectivity and physical activity. However, dense urban areas often amplify pollution and noise exposure, offsetting benefits. Empirical models integrating environmental quality show positive long-run correlations with longevity, emphasizing causal links through reduced oxidative stress and inflammation from cleaner air and water. Overall, modifiable environmental factors explain about 17% of mortality variation, surpassing genetic contributions in large cohort analyses.

Underlying Mechanisms

Key Aging Pathways

The primary biological pathways underlying aging involve interconnected molecular and cellular processes that accumulate damage, impair repair mechanisms, and disrupt . These pathways, often framed as the "," encompass mechanisms causally linked to age-related decline through experimental evidence in model organisms and tissues, including interventions that mitigate them to extend lifespan or healthspan.01377-0) Empirical data from longitudinal studies and genetic manipulations demonstrate their roles, such as deficiencies accelerating aging phenotypes in mice and progeroid syndromes in s. While not exhaustive, twelve core hallmarks have been identified, grouped into primary (damage-initiating), antagonistic (adaptive responses that falter), and integrative (systemic manifestations) categories. Primary hallmarks initiate cellular damage without requiring prior dysfunction. Genomic instability arises from accumulated DNA lesions, including double-strand breaks and mutations, driven by endogenous sources like replication errors and exogenous factors like radiation; deficiencies in repair pathways, such as nucleotide excision repair, correlate with accelerated aging in humans, as seen in xeroderma pigmentosum patients exhibiting premature frailty by age 20-30.01377-0) Telomere attrition shortens chromosome ends with each cell division, limiting replicative potential; in telomerase-deficient mice, this triggers infertility and organ atrophy by mid-adulthood, mimicking human dyskeratosis congenita. Epigenetic alterations involve aberrant DNA methylation, histone modifications, and chromatin remodeling, leading to stochastic gene expression changes; clocks like Horvath's epigenetic age predictor, based on methylation patterns from over 8,000 samples, accurately forecast biological age and mortality risk across tissues.01377-0) Loss of proteostasis reflects impaired protein folding, aggregation, and degradation via chaperones and proteasomes; aggregates like amyloid in Alzheimer's accumulate with age, and proteasome inhibition in worms reduces lifespan by 30-50%. Antagonistic hallmarks represent protective responses that become counterproductive. Deregulated nutrient sensing disrupts pathways like insulin/IGF-1, , and AMPK, promoting anabolic over catabolic states; caloric restriction, which downregulates these, extends lifespan by 20-40% across strains, with genetic inhibition yielding similar gains.01377-0) Mitochondrial dysfunction involves impaired electron transport, ROS overproduction, and mtDNA mutations; shifts in mtDNA, observed in aging human muscles, correlate with , and mitochondrial-targeted antioxidants partially restore function in aged rats. Disabled macroautophagy fails to clear damaged organelles and proteins; inducers like rapamycin extend lifespan in , flies, and by 10-60%, with age-related decline evident in lysosomal accumulation.01377-0) Integrative hallmarks propagate damage across s. entails irreversible growth arrest with a pro-inflammatory secretome (SASP); senolytics clear senescent cells, improving function and extending healthspan in progeroid mice by reducing . exhaustion diminishes regenerative capacity due to quiescence defects and niche alterations; from young donors rejuvenates aged marrow in mice, countering myeloid bias.01377-0) Altered intercellular communication includes disrupted endocrine signaling and inflammaging; circulating factors from young parabionts reverse age-related phenotypes in old mice, such as muscle repair. Chronic inflammation, driven by activation, amplifies damage; IL-6 levels rise exponentially with age in humans, predicting frailty independently of chronological age.01377-0) alters composition, reducing diversity and increasing pathobionts; fecal transplants from young donors improve gut barrier integrity and inflammation in aged mice. These pathways interact causally—for instance, genomic instability fuels , which exacerbates —forming networks amenable to targeted interventions, though human translation remains limited by pleiotropic effects and long trial durations.01377-0) Evidence from studies underscores their relevance, with variants in genes enriching long-lived cohorts.

Evolutionary Explanations for Aging

The prevailing evolutionary perspective holds that aging is not an adaptation but a non-adaptive byproduct of , which favors traits enhancing early-life and over post-reproductive , as the force of selection declines with . This view, rooted in , explains why —progressive physiological decline—manifests despite theoretical potential for negligible aging in species under strong selection. Empirical support derives from comparative studies across taxa, where extrinsic mortality risks inversely correlate with lifespan: high-predation environments select for rapid and shorter lifespans, while low-risk settings permit longer ones. Peter Medawar's mutation accumulation theory, articulated in 1952, posits that mildly deleterious mutations with late-onset effects accumulate via , as weakens after peak reproductive ages when fewer individuals remain to express them. Under this model, early-acting mutations face stringent purging, but late-acting ones persist, eroding fitness in old age; genomic analyses in mammals reveal elevated mutation loads in aging tissues consistent with this drift. Experimental validation includes long-term selection experiments in , where delayed reproduction increased late-life fitness without fully eliminating , implying accumulation of sheltered variants. George Williams extended this framework in 1957 with the , proposing that genes with net positive effects on early —such as enhanced or growth—persist despite deleterious late-life consequences, as selection cannot favor alleles solely beneficial in when reproductive value is low. Genes like p53 exemplify this: tumor suppression aids juvenile survival but may accelerate aging via excessive in later life. Evidence from artificial selection in rodents and insects shows trade-offs, where longevity gains from late-breeding lines incur early-life costs, supporting pleiotropic conflicts over neutral accumulation alone. Quantitative genetic models confirm that such generates age-specific selection gradients driving evolution. Complementing these, Thomas Kirkwood's disposable soma theory (1977) frames aging as a : finite energetic budgets prioritize over indefinite repair, deeming the post-reproductive body "disposable" once is secured. This physiological mechanism aligns with observed fertility-longevity antagonisms in mammals, where caloric restriction extends lifespan but impairs reproduction, and caloric excess accelerates both aging and fecundity decline. Cross-species data, including cetaceans with low extrinsic mortality yet defined , underscore that even protected somas incur maintenance costs exceeding evolutionary returns beyond reproduction. While these theories converge on selection's neglect of late life, debates persist: mutation accumulation emphasizes drift, active trade-offs, and disposable soma mechanistic budgeting, with hybrid models integrating all three via declining selection forces. Empirical tests in and mice reveal partial support for each, but no single theory fully accounts for in aging pathways, prompting refinements incorporating regulatory failures.

Extension Efforts and Interventions

Pharmacological and Genetic Approaches

Pharmacological interventions target conserved aging pathways identified in model organisms, such as inhibition of the mechanistic target of rapamycin () complex 1, activation of (AMPK), and clearance of senescent cells. Rapamycin, an inhibitor, extends median lifespan by 9-14% in mice when administered in mid-life, delaying age-related pathologies including cancer and cognitive decline. In humans, low-dose intermittent rapamycin improves immune function and cardiovascular parameters in older adults, but large-scale trials show limited evidence for broad longevity benefits, with calls for better-designed studies to assess . Metformin, an AMPK activator and drug, decelerates epigenetic aging clocks in non-human and shows geroprotective effects in preclinical models, though human data remain inconclusive pending results from the Targeting Aging with Metformin () trial, a six-year study across 14 U.S. sites evaluating delay of in adults aged 65-79. Senolytics, drugs selectively eliminating senescent cells that accumulate with age and secrete pro-inflammatory factors, extend lifespan by up to 27% and alleviate frailty in . Clinical trials in humans, such as those using plus , demonstrate feasibility and subtle improvements in bone health and physical function in older adults, but effects on overall longevity are unproven, with ongoing studies focusing on age-related diseases like rather than direct lifespan extension. Combinations like trametinib () and rapamycin yield additive lifespan gains in mice, suggesting potential for multi-drug geroprotective regimens, though sex-specific responses—such as stronger effects in males linked to —highlight the need for personalized approaches. These interventions often mimic caloric restriction benefits but face challenges in human translation, including side effects like from and uncertain long-term safety. Genetic approaches leverage heritability estimates of 20-30% for human longevity, focusing on variants in pathways like insulin/IGF-1 signaling and DNA repair. Loss-of-function mutations in genes such as TET2 and ATM correlate with reduced lifespan, while protective alleles in FOXO3 and APOE are enriched in centenarians. Interventions include epigenetic reprogramming using Yamanaka factors to reverse cellular age, which partially restores vision and tissue function in progeroid mice without full tumorigenesis risk. CRISPR-Cas9 screens in neural stem cells identify regulators of proliferative decline, and targeted editing of aging-associated genes like those in telomere maintenance shows promise in ameliorating age-related pathologies in animal models. Gene therapies enhancing telomerase activity extend mouse lifespan by 40% without increasing cancer incidence, but human applications remain preclinical, constrained by delivery challenges, off-target effects, and ethical concerns over germline editing. Overall, while genetic manipulations robustly extend lifespan in short-lived species, translating to humans—where intrinsic limits may cap radical extension—requires rigorous validation beyond correlative studies.

Recent Research Advances (Post-2020)

Research in longevity has accelerated post-2020, with a shift toward clinical translation of interventions targeting , including , epigenetic changes, and nutrient-sensing pathways. Peer-reviewed studies and early-phase trials have focused on s, partial cellular reprogramming, and repurposed drugs like rapamycin, though human evidence remains preliminary and often limited to biomarkers rather than direct lifespan extension. Funding from private biotechs and organizations has driven over 30 trials and initial reprogramming experiments, but systemic biases in —favoring positive preclinical results—necessitate scrutiny of translational gaps. Senolytics, agents selectively clearing senescent cells, advanced through multiple phase II trials post-2020. A 2025 pilot study administered and intermittently to older adults with and slow gait, demonstrating feasibility, safety, and potential reductions in senescent cell markers alongside improved physical function metrics. Similarly, an in early Alzheimer's patients using the same combination reported decreased senescent burden and inflammation, though small sample sizes (n=5) limit generalizability. The SENOLYTICS trial (NCT04685590), a randomized placebo-controlled study, evaluated plus in older adults with frailty, finding no significant adverse events but modest effects on biomarkers and physical . These efforts build on preclinical but highlight challenges like variable senescent cell distribution and off-target effects, with larger trials needed to confirm . Partial reprogramming, using transient expression of Yamanaka factors (e.g., OSK: Oct4, , ), emerged as a promising strategy. A 2024 study in progeroid mice showed OSK-mediated reprogramming extended median lifespan by approximately 40% and maximal lifespan by 32%, restoring tissue function without tumorigenesis by avoiding full pluripotency. Chemical alternatives to viral delivery were explored, enabling reversal in human cells while preserving identity. By 2025, biotech firms advanced toward human trials, with epigenetic assays indicating reduced biological age in treated fibroblasts. However, risks of incomplete reprogramming, such as aberrant , persist, and long-term safety data in non-human primates are sparse. This approach underscores causal links between epigenetic drift and aging but requires rigorous validation beyond mouse models. Rapamycin, an inhibitor, saw expanded human investigation despite equivocal longevity outcomes. The PEARL trial (NCT04488601), ongoing since 2020, assesses low-dose rapamycin's impact on aging in healthy adults, reporting improved immune and metabolic parameters but no direct lifespan data. A 2025 crowdfunded one-year study in middle-aged participants found limited biomarker shifts, with self-reported adherence issues and no clear extension of healthspan metrics. Combinations like rapamycin with trametinib extended mouse lifespan additively by targeting parallel pathways, suggesting synergy potential, yet human trials emphasize side effects like over robust anti-aging proof. Reviews note that while mid-life dosing extends mouse lifespan 9-14%, human evidence prioritizes disease-specific benefits, with cautioned due to inconsistent translation. Emerging tools like AI-driven have accelerated discovery and aging clock development, integrating multi-omics data for predictive models of . Metformin's anti-aging faced , with 2025 analyses questioning its geroprotective effects beyond glucose control in non-diabetics. Overall, post-2020 advances emphasize multimodal strategies, but empirical human data lag preclinical , with survival modeling predicting modest gains (e.g., <15% reaching 100 for females) absent biological shifts. Rigorous, large-scale RCTs remain to distinguish causal interventions from correlative associations.

Animal Model Extensions and Human Translation

Invertebrate and models have demonstrated robust lifespan extensions through interventions targeting conserved aging pathways. For instance, caloric restriction (CR), defined as a 20-40% reduction in intake without , extends median lifespan by up to 50% in and delays age-related pathologies such as cancer and neurodegeneration. Similarly, pharmacological inhibition of the mechanistic target of rapamycin () pathway with rapamycin increases lifespan in mice by 10-20% even when initiated late in life, mimicking effects of dietary restriction across vertebrates including flies and nematodes. Genetic manipulations, such as in C. elegans, activate stress response pathways like FOXO/DAF-16, yielding 2-3 fold lifespan increases, while in mice, interventions like trametinib (a ) combined with rapamycin produce additive extensions of 15-25% in median survival. These models highlight causal roles for nutrient-sensing pathways (e.g., insulin/IGF-1, ) in modulating longevity, with empirical data from controlled, replicable experiments supporting mechanism-specific efficacy. Non-human primates provide closer phylogenetic analogs, yet results are less consistent. In rhesus monkeys, long-term initiated in adulthood improved healthspan markers like reduced incidence of and cancer, correlating with 10-15% survival benefits in one cohort followed for over 20 years. However, a parallel study in another primate cohort showed no significant lifespan extension when began post-maturity, attributing discrepancies to baseline diet quality and . Rapamycin and analogs also extend healthspan in short-tailed macaques by enhancing immune function and reducing , but full lifespan data remain pending due to extended generation times. Translating these findings to humans faces substantial hurdles rooted in interspecies physiological divergences, including metabolic rates, , and evolutionary adaptations to . Only about 5% of preclinical therapies demonstrating efficacy in animal models achieve regulatory approval for use, with longevity interventions particularly prone to due to compressed timelines in versus decades-long aging trajectories. trials of , such as the CALERIE study (2015-2023), revealed a 2-3% reduction in the pace of biological aging via DNA methylation clocks after two years of 12-15% restriction, alongside improved metabolic markers, but lacked direct lifespan endpoints and reported adherence challenges. For rapamycin, phase II trials in elderly s (e.g., 2014-2018) enhanced responses and reduced infection rates by 20-30%, suggesting delayed immunologic aging, yet no randomized data confirm lifespan or broad healthspan extension, with side effects like limiting chronic dosing. Proposed trials like (Targeting Aging with Metformin) aim to assess delayed as a proxy for longevity, but remains tentative absent century-scale follow-up, underscoring the need for that predict outcomes beyond animal proxies. Overall, while animal data causally link pathway modulation to extended vitality, evidence is correlative and preliminary, tempered by translational inefficiencies observed across biomedical fields.

Controversies and Realities

Skepticism on Radical Life Extension

S. Jay Olshansky, a gerontologist at the University of Illinois at Chicago, argues that radical life extension—defined as substantial increases in remaining far beyond historical norms—is implausible in the without unprecedented breakthroughs in slowing the aging process itself. In a 2024 analysis published in Nature Aging, Olshansky and colleagues examined cohort mortality data from high-income nations, forecasting that even under optimistic scenarios, survival to age 100 will remain below 15% for females and 5% for males, with average plateauing around 85 years. This skepticism stems from the observation that 20th-century gains of approximately 30 years in at birth were primarily driven by reductions in early-life mortality from infectious diseases and infant deaths, rather than extensions of maximum lifespan, which has increased only modestly from the low 70s to the high 70s or low 80s in most populations. Historical trends reinforce this view, as gains in have decelerated since the , with recent data showing outright declines in places like the due to factors including the , opioid overdoses, and chronic diseases, though the underlying pattern predates these events. studies indicate that individuals born in 1980 are unlikely to reach an average of 100 years, consistent with the Gompertz-Makeham law of mortality, which describes an exponential increase in death rates with age after early adulthood, reflecting accumulated biological vulnerabilities that compound over time. This law, empirically validated across human populations and species, implies that interventions must counteract not just single diseases but the systemic frailty that accelerates mortality in later decades, a challenge unmet by current medical paradigms focused on disease-specific treatments. Translational failures further underpin skepticism, as anti-aging interventions successful in short-lived animal models—such as caloric restriction or drugs like rapamycin extending lifespan by 20-30%—have not yielded comparable outcomes due to profound physiological differences, including metabolic rates, reproductive cycles, and environmental exposures. Over 92% of preclinical therapies tested in animals fail to advance successfully in trials, a rate unchanged for decades, highlighting the limitations of extrapolating from with 2-3 year lifespans to humans whose aging unfolds over 80+ years. Critics like Olshansky emphasize that without geroscience advances targeting core aging hallmarks—such as (epitomized by the , where cells divide finitely before arresting)—incremental health improvements will compress morbidity but not radically extend vitality. While proponents of radical extension invoke concepts like "," skeptics counter that such optimism overlooks empirical ceilings observed in supercentenarians, where the oldest verified age remains 122 years (, 1875-1997), with no cohort approaching routine surpassing of 110. This stasis aligns with evolutionary theories positing that negligible selection pressure post-reproduction permits aging as a of early-life fitness trade-offs, rendering comprehensive reversal biologically arduous absent engineered overrides of entrenched genetic programs. Recent forecasts across multiple models confirm deceleration in life expectancy improvements for living cohorts, suggesting that societal investments in anti-aging may yield healthspan gains but not the transformative lifespan doublings hyped in some circles.

Criticisms of the Anti-Aging Industry

The anti-aging industry, encompassing supplements, cosmetics, and biotech interventions marketed to combat aging, faces substantial criticism for overhyped claims that often outpace empirical evidence. Scientific skeptics argue that many purported longevity enhancers, such as certain peptides and stem cell therapies, represent "snake oil" that undermines credible research by promising rapid reversal of aging without robust clinical validation. Dermatologists and regulators highlight that cosmetic products frequently make unsubstantiated anti-wrinkle or rejuvenation assertions, blurring lines between cosmetics and unapproved drugs, which leads to consumer deception. Regulatory bodies like the U.S. (FDA) have issued numerous warning letters to companies for illegal drug claims in anti-aging products, including topical creams and supplements purporting to treat or prevent age-related decline. The 's Health Product Database lists various unapproved anti-aging items as violative, often citing false promises without or effectiveness data from controlled trials. Critics note that the absence of a defined regulatory pathway for aging-targeted therapies—since the does not classify aging itself as a treatable —exacerbates issues, allowing off-label or investigational promotions to flourish unchecked while delaying legitimate approvals. Financial exploitation is another focal point, with the industry accused of preying on fears of mortality through high-cost, low-evidence offerings. For instance, anti-aging supplements have been flagged in alerts for making sweeping longevity guarantees without refund mechanisms, disproportionately targeting older adults. Peer-reviewed analyses reveal inflated pricing for products like retinoids or antioxidants, where unit costs far exceed proven benefits, fostering about value versus marketing-driven demand. Internal field debates, including among longevity scientists, underscore tensions where venture-backed hype clashes with incremental progress, as seen in disputes involving prominent researchers like Leonard Guarente. Ethical concerns amplify these critiques, with detractors arguing that unverified interventions risk health hazards, such as undisclosed chemical toxicities in beauty products linked to endocrine disruption. Nobel laureate has voiced alarm over exaggerated research narratives that mislead public expectations and divert resources from grounded geroscience. While genuine advances in model organisms exist, the industry's blend of and premature commercialization erodes trust, as thousands of past remedies have failed rigorous testing, reinforcing calls for stricter evidence standards.

Comparative Longevity

Long-Lived Non-Human Species

The ocean quahog clam (), a bivalve mollusk native to the North Atlantic, demonstrates the longest verified lifespan among non-clonal metazoans, with a specimen named Ming aged at 507 years through annual growth ring counts in its shell and confirmatory radiocarbon analysis of those rings. This individual, collected off in 2006, highlights the clam's capacity for incremental growth over centuries in cold, stable deep-sea environments, where predation is minimal and metabolic demands low. Such longevity arises from efficient mechanisms and resistance to , as evidenced by low rates of shortening observed in related studies of the . Among vertebrates, the (Somniosus microcephalus) exhibits the longest lifespan, with of eye lens protein cores from 28 specimens indicating a minimum age of 272 years and an estimated maximum of 392 years (with a 95% of 272–512 years). These predators, reaching only after 150 years, benefit from ectothermic in frigid waters, which slows molecular damage accumulation; recent genomic analyses reveal expanded gene families for and toxin resistance, potentially underlying their durability. The (Balaena mysticetus), an cetacean, achieves lifespans exceeding 200 years, with confirmed ages up to 211 years derived from eye lens and embedded fragments from historical . Genetic sequencing has identified adaptations such as enhanced cancer suppression genes (e.g., variants) and efficient oxygen transport, enabling these massive mammals to withstand physiological stresses over decades despite high body mass. Terrestrial reptiles like the (Chelonoidis niger) attain captive lifespans of up to 177 years, as recorded for individuals like Harriet, verified through historical documentation and growth annuli in scutes. Their longevity stems from , low extrinsic mortality in island habitats, and physiological traits including robust defenses and delayed reproductive . These collectively illustrate that extended lifespans correlate with environmental stability, reduced metabolic rates, and evolved protections against genomic instability, offering comparative models for investigating aging pathways conserved across taxa.

Insights from Plants and Other Organisms

Plants exhibit modular growth patterns that enable indefinite lifespan in favorable conditions, contrasting with the programmed senescence typical in many animals. Unlike unitary organisms, plants continuously produce new meristematic tissues—undifferentiated stem cells at apices and cambium—that generate organs throughout life, replacing senescing parts without systemic decline. This architecture allows species like the bristlecone pine (Pinus longaeva) to persist for over 5,000 years by compartmentalizing damage and maintaining low metabolic rates in harsh environments, with pollen studies showing no age-related mutation accumulation. Similarly, the ginkgo (Ginkgo biloba) achieves lifespans exceeding 3,000 years through sustained cambial activity and epigenetic stability, including DNA methylation patterns that regulate gene expression without progressive deterioration. Clonal reproduction further extends plant longevity beyond individual genets. Colonies of genetically identical ramets, formed via vegetative propagation, evade reproductive ; the quaking aspen (Populus tremuloides) clone "Pando" in spans over 43 hectares and is estimated at 14,000 to 80,000 years old, with root systems sustaining periodic shoot turnover despite ramet mortality from external factors. Such immortality is not absolute, as genets eventually succumb to accumulated somatic mutations or environmental catastrophes, but the absence of a strict —due to persistent activity in meristems—permits millennia-scale persistence absent in most animals. Hormonal mechanisms underpin this resilience. Cytokinins and gibberellins antagonize by promoting and delaying chlorophyll breakdown; their exogenous application extends post-harvest longevity in cut greens, suggesting endogenous gradients regulate whole-plant aging. In long-lived species, sustained cytokinin signaling in meristems prevents exhaustion, while gibberellins support vascular continuity. Stress responses, including from mild adversity, enhance defenses via secondary metabolites like polyphenols, which stabilize proteomes and mitigate oxidative damage—parallels explored in models for mitochondrial support and reduction. Insights for derive from ' regenerative capacity and leaky germline-soma barrier, where cells routinely dedifferentiate into totipotent states, enabling whole-organism —a feat impossible in vertebrates due to epigenetic locks. This informs therapies, as quiescence under stress mirrors potential human interventions to preserve progenitor pools. However, translational limits persist: lack centralized organs vulnerable to failure, and their poikilothermic metabolism avoids caloric accumulation driving human pathologies. Empirical data from models underscore causal roles for continuous renewal over mere size or caloric restriction, challenging anthropocentric aging paradigms without implying direct feasibility. Among other organisms, colonial fungi and exhibit analogous modularity. Ancient fungal clones, like in spanning 2,400 years and 965 hectares, achieve persistence through mycelial networks that redistribute resources, evading localized decay via compartmentalization—mechanisms akin to plant vascular systems. Lichens, symbiotic algal-fungal consortia, endure millennia in extreme niches by alternating and activation, with low metabolic rates and proficiency preventing mutational load. These systems highlight distributed architectures as longevity enablers, informing bioengineering of resilient human tissues, though species-specific physiologies preclude universal application.

Persistent Myths

Debunked Claims and Pseudoscience

Claims of exceptional human longevity in so-called "Blue Zones"—regions purportedly fostering supercentenarians through lifestyle factors—have been largely refuted by analyses revealing systemic errors in vital records, including pension fraud, familial exaggeration, and incomplete documentation rather than genuine biological outliers. Researcher Saul Justin Newman demonstrated that extreme age validations in areas like Okinawa, Sardinia, and Nicoya correlate with socioeconomic poverty and lax record-keeping, not verifiable longevity, with many centenarian claims collapsing under scrutiny of birth/death discrepancies. These findings, awarded an Ig Nobel Prize in 2024, underscore how uncritical acceptance of anecdotal data in popular media and books has propagated pseudoscientific narratives, ignoring empirical validation requirements. Human growth hormone (HGH) supplementation for anti-aging has been promoted by clinics claiming reversal of age-related decline, but federal regulations deem such uses illegal outside approved indications like growth deficiencies, with no rigorous evidence supporting lifespan extension or broad rejuvenation. The U.S. has issued warnings against over-the-counter HGH products marketed for longevity, citing lack of proof for efficacy and potential risks like and joint disorders, based on controlled trials showing benefits confined to specific deficiencies rather than general aging. A 2003 review highlighted that promotional studies often involved small, non-randomized cohorts, failing to demonstrate causal links to extended healthspan. Regenerative medicine claims involving stem cells or exosomes for anti-aging—touted to regenerate tissues and prolong life—lack FDA approval and rest on preclinical or anecdotal data without human trials confirming safety or efficacy for longevity endpoints. FDA consumer alerts from 2020 emphasize that such unproven therapies, often from clinics, pose risks like tumor formation without delivering promised , as Phase I/II trials have shown inconsistent engraftment and no population-level lifespan impacts. Peer-reviewed critiques note that hype around these interventions stems from extrapolated animal models, ignoring translational failures due to human immune complexities. Sirtuin-activating compounds like , initially hyped for mimicking caloric restriction and extending lifespan via epigenetic mechanisms, failed to replicate in key model organisms; a multi-institution study across seven labs found no lifespan extension in or flies, refuting earlier single-lab claims. Subsequent human trials, including large randomized controlled studies up to 2022, showed negligible metabolic or aging improvements, attributing initial enthusiasm to artifacts and favoring positive results. This exemplifies pseudoscientific overreach in longevity, where preliminary data drives commercial supplements despite contradictory evidence from higher-fidelity models.

References

  1. [1]
    Aging and Longevity: Why Knowing the Difference Is Important ... - NIH
    Feb 28, 2011 · Longevity is the length of the life span independent of the biological aging process. This brief commentary will provide justification for these ...Missing: gerontology | Show results with:gerontology
  2. [2]
    Longevity, Biological - Carnes - Wiley Online Library
    Dec 21, 2015 · Longevity is an essential part of how organisms adapt to the risks that endanger life or reproduction. Aging and longevity are quite different ...
  3. [3]
    Life Expectancy - Our World in Data
    Across the world, people are living longer. In 1900, the average life expectancy of a newborn was 32 years. By 2021 this had more than doubled to 71 years.Life expectancy: what does this · Twice as long · Than in other rich countries? · Has
  4. [4]
    4 things to know about the latest global population trends - UN.org.
    Sep 5, 2024 · Global life expectancy at birth reached 73.3 years in 2024, having fallen from 72.6 in 2019 to 70.9 at the peak of the pandemic in 2020 and 2021 ...
  5. [5]
    Lifespan and Healthspan: Past, Present, and Promise - PMC - NIH
    At first, this increasing length of life resulted from declines in infectious disease and deaths concentrated among the young. After most deaths from infectious ...
  6. [6]
    Human Lifespan Definition & What To Know - Cleveland Clinic
    Nov 11, 2024 · Right now, the maximum human lifespan is 122 years. Experts base that lifespan on the longest-lived person with a verifiable date of birth.
  7. [7]
    Implausibility of radical life extension in humans in the twenty-first ...
    Oct 7, 2024 · Survival to the age of 122.45 years—the maximum lifespan observed for humans as determined by the documented survival of Jeanne Calment, who ...
  8. [8]
    Rapamycin for longevity: the pros, the cons, and future perspectives
    Jun 19, 2025 · Rapamycin administration initiated in mid-life extends lifespan by 9%–14% in mice and is associated with delayed onset of age-related ...
  9. [9]
    The Longevity Med Summit: insights on healthspan from cell to society
    Jul 16, 2024 · Longevity research, also referred to as geroscience (Larsen, 2017), employs a multidisciplinary scientific approach to understanding the ...
  10. [10]
    Debate on human aging and lifespan - PMC - PubMed Central
    538 (October 13, 2016), the authors concluded that human lifespan is limited to 115 years and the probability of a lifetime exceeding 125 in any given year is ...
  11. [11]
    Life expectancy may be reaching upper limits—for now
    Oct 21, 2024 · A: The study looks back at advances in human life expectancy made between 1990 and 2019 in a number of countries where people typically live ...
  12. [12]
    Despite medical advances, life expectancy gains are slowing
    Oct 7, 2024 · Life expectancy at birth in the world's longest-living populations has increased only an average of six and a half years since 1990, the analysis found.<|control11|><|separator|>
  13. [13]
    What do the terms life expectancy, lifespan, longevity and health ...
    The term longevity describes the ability to live a long life beyond the species-specific average age at death [De Benedictis & Franceschi 2006]. Longevity can ...
  14. [14]
    The Diversity of Longevity Metrics (Chapter 3)
    Nov 14, 2024 · Metrics such as life expectancy and percentile longevities can only be computed for samples in which the full age-at-death distribution is known ...
  15. [15]
    Life expectancy at birth (years) - World Health Organization (WHO)
    Definition: The average number of years that a newborn could expect to live, if he or she were to pass through life exposed to the sex- and age-specific ...
  16. [16]
    Healthy life expectancy (HALE) at birth
    Healthy life expectancy (HALE) is the average number of years a person can expect to live in "full health", considering years lived in less than full health.
  17. [17]
    How to measure biological aging in humans | Nature Medicine
    Feb 26, 2025 · It was first demonstrated that chronological age can be predicted with remarkable precision through specific DNA methylation patterns. The ...
  18. [18]
    Lifespan - an overview | ScienceDirect Topics
    Lifespan is defined as the length of life, which can be measured as average lifespan and maximum lifespan; average lifespan is typically increased by ...
  19. [19]
    NVSS - Life Expectancy - CDC
    Life expectancy is the average years a person at a given age can expect to live, calculated using life tables that measure mortality and survivorship.
  20. [20]
    Life Expectancy - FastStats - CDC
    Data are for the U.S.. Life expectancy at birth. Both sexes: 78.4 years; Males: 75.8 years; Females: 81.1 years. Source: ...
  21. [21]
    Healthy People - HP2020 Foundation Health Measures - CDC
    Feb 9, 2022 · Life expectancy is defined as the average number of years a group of persons are expected to survive from a given starting age.
  22. [22]
    Mayo Clinic Q and A: Lifespan vs. healthspan
    Sep 14, 2024 · Lifespan refers to the total number of years a person lives, from birth to death. Healthspan is a concept that focuses on the number of those years that a ...
  23. [23]
    [PDF] Maximizing Healthspan - The University of Alabama at Birmingham
    Healthspan is a term coined by the National Institute on Aging to emphasize the importance of the distinction between quality vs. quantity of life. For ...
  24. [24]
    Global Healthspan-Lifespan Gaps Among 183 World Health ...
    Dec 11, 2024 · The difference in life expectancy and health-adjusted life expectancy (ie, healthspan-lifespan gap) represents the number of years lived with ...Missing: distinctions | Show results with:distinctions
  25. [25]
    Too well to die; too ill to live: an update on the lifespan versus health ...
    May 12, 2025 · The debate between lifespan (the total number of years a person lives) and health span (the period of life free from chronic disease or disability)
  26. [26]
    Healthspan-lifespan gap differs in magnitude and disease ... - Nature
    Sep 1, 2025 · The difference between the number of years lived (lifespan) and the number of years lived in good health (healthspan) is known as the healthspan ...
  27. [27]
    (PDF) Patterns of death, 1800–2020 - ResearchGate
    The period witnessed enormous and ubiquitous rises in life expectancy at birth, from a global average of perhaps 30 years in 1800 to an estimated average of 72 ...
  28. [28]
    Why Life Expectancy Skyrocketed in Early 20th-Century America
    Oct 14, 2025 · Life Expectancy Rises as Child Mortality Rates Fall​​ As parents learned to protect their children from disease, child mortality rates began ...
  29. [29]
    Demographic perspectives on the rise of longevity - PNAS
    Hence, it can be concluded that human life expectancy before 1840 generally fell below 40, and in situations of famine, epidemic, or war, the value could be ...<|separator|>
  30. [30]
    GHE: Life expectancy and healthy life expectancy
    Global life expectancy has increased by more than 6 years between 2000 and 2019 – from 66.8 years in 2000 to 73.1 years in 2019.Life expectancy at birth (years) · HALE · Healthy life expectancy (HALE...
  31. [31]
    Longevity Around the Turn of the 20th Century: Life-Long Sustained ...
    Mar 27, 2018 · Until 1950, the average increase in life expectancy could mainly be attributed to improved living conditions and better healthcare, causing a ...
  32. [32]
    [PDF] World Population Prospects 2024: Summary of Results
    Globally, life expectancy at birth reached 73.3 years in 2024, an increase of 8.4 years since 1995. Further reductions in mortality are projected to result in ...<|separator|>
  33. [33]
    Causes of America's Lagging Life Expectancy - NIH
    Together, injuries (drug overdose, firearm-related deaths, motor vehicle accidents, homicide), circulatory diseases, and mental disorders/nervous system ...
  34. [34]
    Study shows life expectancy stagnation in Europe - News-Medical
    Feb 18, 2025 · "We found that deaths from cardiovascular diseases were the primary driver of the reduction in life expectancy improvements between 2011–19.
  35. [35]
    Life Expectancy by Country 2025 - World Population Review
    84.4 Age. 2024. United Nations Data World Bank Data. Country. Life Expectancy UN 2024↓. Female Life Expectancy UN 2024. Male Life Expectancy UN 2024. Monaco ...
  36. [36]
    How does U.S. life expectancy compare to other countries?
    Jan 31, 2025 · Life expectancy at birth in the U.S. increased 0.9 years from 2022 to 78.4 in 2023. In comparable countries, life expectancy was 82.5, which is, ...
  37. [37]
    Healthy life expectancy at birth (years) - WHO Data
    Aug 2, 2024 · Worldwide, healthy life expectancy at birth (years) has improved by 3.79 years from 58.1 [57.4 - 58.8] years in 2000 to 61.9 [61 - 62.7] years in
  38. [38]
    2024: the United Nations publishes new world population projections
    Global life expectancy at birth, which rose from 64.0 years in 1990 to 73.3 in 2024, should continue to rise—to as high as 77.0 in 2050. And differences between ...
  39. [39]
    Global life expectancy to increase by nearly 5 years by 2050 despite ...
    May 17, 2024 · Global life expectancy is forecasted to increase from 73.6 years of age in 2022 to 78.1 years of age in 2050 (a 4.5-year increase). Life ...
  40. [40]
    Life expectancy, including UN projections - Our World in Data
    This includes the observed lifeexpectancy since 1950, and the medium-variant projections for thefuture, based on estimates by the UN Population Division.
  41. [41]
    World Supercentenarian Rankings List | Gerontology Research Group
    those aged 110 or older.Supercentenarians · Recent validations · Recent deaths · Ethel Caterham
  42. [42]
  43. [43]
    Oldest person ever | Guinness World Records
    The greatest fully authenticated age to which any human has ever lived is 122 years 164 days by Jeanne Louise Calment (France).
  44. [44]
    Jeanne Calment: Validation of the Duration of Her Life
    Jeanne Calment died on the fourth of August, 1997. She was then 122 years old. We validated her age when she entered her 121st year of life.<|separator|>
  45. [45]
    Was Jeanne Calment the Oldest Person Who Ever Lived—or a Fraud?
    Feb 10, 2020 · After the woman died, at a hundred and sixteen, in 1991, Calment became the oldest person ever known to have lived.
  46. [46]
    Oldest living people | Gerontology Wiki - Fandom
    This is a list of the oldest living people in the world. Supercentenarians that are categorized as "validated" have had their ages authenticated.
  47. [47]
    List of oldest living people - Wikipedia
    It was estimated in 2015 that between 150 and 600 living people had reached the age of 110. The true number is uncertain, as not all supercentenarians ...
  48. [48]
    Supercentenarians – The Conquerors of Aging - DiVA portal
    Sep 24, 2024 · The results indicate that the number of supercentenarians has increased quickly over time, that 90% of validated supercentenarians are female ...Missing: demographics | Show results with:demographics
  49. [49]
    Genetic, Socioecological, and Health Determinants of Extreme ...
    To provide an overview of global demographic trends and patterns among supercentenarians, including geographic distribution, gender prevalence, and ...
  50. [50]
    The Genetics of Extreme Longevity: Lessons from the New England ...
    Nov 29, 2012 · One of our hypotheses about the genetic make-up of exceptional longevity was that a relative lack of disease-associated variants could in part ...
  51. [51]
    Characteristics of 32 Supercentenarians - PMC - NIH
    Given that longevity has been associated with years of education, the change in years of required education, in combination with improved public health and ...
  52. [52]
    Human longevity is influenced by many genetic variants
    Variation in human lifespan is 20 to 30% heritable in twins but few genetic variants have been identified. We undertook a Genome Wide Association Study ...
  53. [53]
    a population-based study of 2872 Danish twin pairs born 1870-1900
    The heritability of longevity was estimated to be 0.26 for males and 0.23 for females, suggesting it is moderately heritable.
  54. [54]
    Heritability of human lifespan is about 50% when confounding ...
    Apr 21, 2025 · Current estimates of heritability are low - twin studies show that about 20-25% of the variation in lifespan is explained by genetics, and some ...
  55. [55]
    New England Centenarian Study - Boston University Medical Campus
    Genes play a critical and complex role in facilitating exceptional longevity. The genetic influence becomes greater and greater with older and older ages, ...
  56. [56]
    A meta-analysis of genome-wide association studies identifies ...
    Aug 14, 2019 · Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA ...
  57. [57]
    A Genome-Wide Association Study of 2304 Extreme Longevity ...
    Dec 21, 2022 · We performed a genome-wide association study (GWAS) of human extreme longevity (EL), defined as surviving past the 99th survival percentile, ...
  58. [58]
    Rare genetic associations with human lifespan in UK Biobank are ...
    Feb 28, 2025 · Previous genome-wide association studies (GWAS) have identified over 20 associated loci including APOE, CHRNA3/5, HLA-DQA1 and LPA. Recently, a ...
  59. [59]
    Depletion of loss-of-function germline mutations in centenarians ...
    Oct 19, 2024 · Our findings suggest that a protective genetic background, characterized by a reduced burden of damaging variants, contributes to exceptional longevity.
  60. [60]
    Genetics of human longevity: From variants to genes to pathways
    Nov 8, 2023 · Gene set analysis of GWAS data for human longevity highlights the relevance of the insulin/IGF-1 signaling and telomere maintenance pathways.Introduction · Heritability of longevity · Current approaches to... · Conclusions
  61. [61]
    The Genetics of Exceptional Longevity: Insights From Centenarians
    Many genetic variations known to affect life expectancy exist in centenarians. This review of studies conducted on centenarians and supercentenarians (older ...
  62. [62]
    Genomics of 1 million parent lifespans implicates novel ... - eLife
    Jan 15, 2019 · (2016) Human longevity is influenced by many genetic variants: evidence from 75,000 UK biobank participants. Aging 8:547–560. https://doi.org ...
  63. [63]
    Cellular aging (the Hayflick limit) and species longevity - PubMed
    A model is presented which proposes a specific cause-and-effect relationship between a limited cell division potential and the maximum lifespan of humans and
  64. [64]
    Telomere shortening rate predicts species life span - PNAS
    Jul 8, 2019 · Telomere shortening to a critical length can trigger aging and shorter life spans in mice and humans by a mechanism that involves induction ...
  65. [65]
    Telomeres and Longevity: A Cause or an Effect? - PMC - NIH
    Jul 1, 2019 · Telomeres, the caps that protect the end of linear chromosomes, are known to shorten with age, inducing cell senescence and aging.
  66. [66]
    Deciphering death: a commentary on Gompertz (1825) 'On the ... - NIH
    The idea that the Gompertz model might constitute a fundamental 'law of mortality' has given way to the recognition that other patterns exist, not only across ...
  67. [67]
    Longitudinal analysis of blood markers reveals progressive loss of ...
    May 25, 2021 · We conclude that the criticality resulting in the end of life is an intrinsic biological property of an organism that is independent of stress factors.
  68. [68]
    Are We Approaching a Biological Limit to Human Longevity? - PMC
    Despite these findings suggesting possible provisional limits to human longevity, there is still no conclusive evidence for inevitable fixed biological limit ...
  69. [69]
    Impact of Healthy Lifestyle Factors on Life Expectancy and Lifetime ...
    Jul 17, 2024 · Adopting a healthy lifestyle is associated with a longer life expectancy and a reduction of health care expenditure in Taiwanese adults.
  70. [70]
    Life expectancy can increase by up to 10 years following sustained ...
    Nov 20, 2023 · Adherence to healthy dietary patterns can prevent the development of non-communicable diseases and affect life expectancy.
  71. [71]
    Smoking Cessation and Short- and Longer-Term Mortality
    Feb 8, 2024 · Cessation by 40 years of age averts 90% of the lifetime risk of mortality attributable to smoking compared with continued smoking.
  72. [72]
    The Benefits of Quitting Smoking at Different Ages
    Jun 25, 2024 · For example, 52.8% of 35-year-old individuals who quit smoking at age 35 will gain at least 1 year in life expectancy and 36.0% will gain at ...
  73. [73]
    Does Physical Activity Increase Life Expectancy? A Review of ... - NIH
    Results of 13 studies describing eight different cohorts suggest that regular physical activity is associated with an increase of life expectancy by 0.4 to 6.9 ...
  74. [74]
    How much resistance exercise is beneficial for healthy aging ... - NIH
    Recent meta-analyses reveal a U-shaped relationship between RE volumes and mortality, with optimal benefits achieved at about 60 min of RE per week.
  75. [75]
    The Relationship Between Exercise and Longevity: Challenging the ...
    Jul 8, 2025 · Further supporting a longevity benefit at high volume of exercise is a systematic review and meta-analysis of 48 studies by Blond, et al., which ...
  76. [76]
    Physical Activity Volume, Intensity, and Mortality: Harmonized Meta ...
    The total volume of physical activity was associated with a lower risk of mortality to a greater extent than the contribution of MVPA to physical activity ...
  77. [77]
    Estimating impact of food choices on life expectancy: A modeling study
    Feb 8, 2022 · We have developed a decision support model that predicts how dietary choices affect life expectancy (LE).
  78. [78]
    Life expectancy gains from dietary modifications: a comparative ...
    Aug 17, 2024 · We aimed to estimate the increase in life expectancy resulting from the transition from typical national dietary patterns to longevity-optimizing dietary ...
  79. [79]
    Calorie Restriction Slows Pace of Aging in Healthy Adults
    Feb 9, 2023 · Calorie restriction, a proven intervention to slow aging in animals, showed evidence of slowing the pace of biological aging in a human randomized trial.
  80. [80]
    Calorie restriction for enhanced longevity: The role of novel dietary ...
    Calorie restriction (CR) without malnutrition is the most effective non-pharmacological intervention that enhances longevity and healthspan in numerous nonhuman ...
  81. [81]
    Effect of long-term caloric restriction on DNA methylation measures ...
    Feb 9, 2023 · We found that CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in ...<|separator|>
  82. [82]
    Sleep Duration and All-Cause Mortality: A Systematic Review ... - NIH
    Both short and long duration of sleep are significant predictors of death in prospective population studies.
  83. [83]
    Sleep regularity is a stronger predictor of mortality risk than sleep ...
    Abstract. Abnormally short and long sleep are associated with premature mortality, and achieving optimal sleep duration has been the focus of sleep health.Abstract · Methods · Results · Discussion
  84. [84]
    Relationship of Sleep Duration With All‐Cause Mortality and ...
    Sep 9, 2017 · Our findings indicate that both short and long sleep duration is associated with an increased risk of all‐cause mortality and cardiovascular events.
  85. [85]
    Physical activities, longevity gene, and all-cause mortality among ...
    Jul 1, 2025 · Our study shows that participation in leisure activities reduces mortality risk by 15%, which is higher than the 7% risk reduction associated ...Study Design And... · Statistical Analyses · Longevity Genetic Risk...
  86. [86]
    The Association Between Income and Life Expectancy in the United ...
    Some studies suggest a reduction in life expectancy for women of low socioeconomic status in recent years, but the robustness of this conclusion has been ...
  87. [87]
    Determinants of inequalities in life expectancy - The Lancet
    The risk factors contributing most to the gap in life expectancy were smoking (19·8% among men and 18·9% among women), low income (9·7% and 13·4%), and high ...
  88. [88]
    Socioeconomic differences in working life expectancy: a scoping ...
    Mar 7, 2024 · Workers with low socioeconomic position were more prone to earlier exit from the labour market even after controlling for ill-health [25].
  89. [89]
    Socioeconomic development and life expectancy relationship - Genus
    Jan 10, 2020 · The main results are that higher values of GDP per capita and lower values of infant mortality levels lead to higher life expectancy at birth ...
  90. [90]
    The rising income gradient in life expectancy in Sweden over six ...
    Mar 31, 2025 · This study reveals that the income gradient in life expectancy in Sweden has steadily increased since the 1960s, despite a reduction in income inequality until ...
  91. [91]
    Loss of life expectancy from air pollution compared to other risk factors
    Sep 1, 2020 · Global excess mortality from all ambient air pollution is estimated at 8.8 (7.11-10.41) million/year, with an LLE of 2.9 (2.3-3.5) years, being a factor of two ...
  92. [92]
    Air pollution takes 2 years off average global life expectancy - CNBC
    Jun 14, 2022 · Air pollution, which is primarily the result of burning fossil fuels, takes 2.2 years of the global life expectancy for each person, according ...
  93. [93]
    Polluted Air Shortens Human Lifespans More Than Tobacco, Study ...
    Aug 28, 2023 · ... air pollution as the world's top threat to public health, responsible for reducing average life expectancy by 2.3 years worldwide. China ...
  94. [94]
    How does the environment affect human ageing? An ...
    Oct 15, 2020 · Climate is therefore a tolerance factor relating to longevity with a moderate climate being more conducive to human longevity than extreme ...
  95. [95]
    Centenarian study suggests living environment may be key to ...
    Jun 17, 2020 · The research team's findings suggest that Washingtonians who live in highly walkable, mixed-age communities may be more likely to live to their 100th birthday.Missing: empirical | Show results with:empirical
  96. [96]
    Life expectancy and the environment - ScienceDirect.com
    Our model produces a positive correlation between longevity and environmental quality, both in the long-run and along the transition path.<|separator|>
  97. [97]
    Lifestyle and environmental factors affect health and ageing more ...
    Feb 20, 2025 · environmental factors explained 17% of the variation in risk of death, compared to less than 2% explained by genetic predisposition (as we ...Missing: empirical | Show results with:empirical
  98. [98]
    Hallmarks of aging: An expanding universe - PubMed
    Jan 19, 2023 · We propose the following twelve hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled ...
  99. [99]
    Hallmarks of aging: An expanding universe - Cell Press
    Jan 19, 2023 · We propose the following twelve hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, ...
  100. [100]
    Molecular mechanisms of aging and anti-aging strategies
    May 24, 2024 · Aging is a complex and multifaceted process involving a variety of interrelated molecular mechanisms and cellular systems.
  101. [101]
    The evolution of ageing: classic theories and emerging ideas - PMC
    Oct 29, 2024 · Ageing is generally regarded as a non-adaptive by-product of evolution. Based on this premise three classic evolutionary theories of ageing ...
  102. [102]
    The Evolution of Aging | Learn Science at Scitable - Nature
    Top (A): Mutation Accumulation. Medawar realized that, if the force of selection declines with age, mutations or alleles that are neutral (i.e., have no effect) ...
  103. [103]
    The evolution of aging and lifespan - Cell Press
    Aug 10, 2023 · Evolutionary theory predicts that aging is an inevitable result of the increased selective impact of genes that influence early-life survival ...
  104. [104]
    Molecular footprint of Medawar's mutation accumulation process in ...
    May 6, 2019 · Medawar's mutation accumulation hypothesis explains aging by the declining force of natural selection with age: Slightly deleterious germline ...
  105. [105]
    A test of evolutionary theories of aging - PMC
    The two leading theories posit that aging is due to (i) pleiotropic genes with beneficial early-life effects but deleterious late-life effects.
  106. [106]
    Is antagonistic pleiotropy ubiquitous in aging biology? - PMC - NIH
    Antagonistic pleiotropy, as it applies to aging, hypothesizes that animals possess genes that enhance fitness early in life but diminish it in later life.
  107. [107]
    Antagonistic Pleiotropy and p53 - PubMed - NIH
    George Williams' antagonistic pleiotropy theory of aging proposes that cellular damage and organismal aging are caused by pleiotrophic genes.
  108. [108]
    The disposable soma theory of aging in reverse | Cell Research
    Nov 5, 2013 · These ideas were formalized by Thomas Kirkwood in the disposable soma theory of aging. For the last several decades the aging research ...
  109. [109]
    Human longevity at the cost of reproductive success - PubMed
    The disposable soma theory on the evolution of ageing states that longevity requires investments in somatic maintenance that reduce the resources available ...
  110. [110]
    Horizons in the evolution of aging - BMC Biology - BioMed Central
    Aug 20, 2018 · Classic theories of aging pertain mainly to relatively short-lived species with increasing mortality and decreasing fertility after maturity, ...The Evolution Of Aging In... · Some Mechanisms Of Aging Are... · Trade-Offs With Lifespan Are...
  111. [111]
    Consolidating multiple evolutionary theories of ageing suggests a ...
    We consolidate multiple evolutionary theories of ageing and discuss data supporting hyper/hypofunctional changes at a global molecular and functional level in ...
  112. [112]
    Rapamycin Shows Limited Evidence for Longevity Benefits in ...
    Sep 24, 2025 · The findings point to the urgent need for larger, better-designed human trials before recommending rapamycin for off-label use to prevent aging.
  113. [113]
    What is the clinical evidence to support off-label rapamycin therapy ...
    Aug 7, 2025 · Low dose rapamycin therapy has been proposed as a longevity candidate in healthy aging adults. We present a review of the evidence for low dose ...
  114. [114]
    Metformin: decelerates biomarkers of aging clocks - Nature
    Nov 13, 2024 · A recent study published in Cell shows the widely known and used antidiabetic drug metformin, has geroprotective benefits in non-human male primates.
  115. [115]
    TAME - Targeting Aging with Metformin
    The Targeting Aging with Metformin (TAME) Trial is a series of nationwide, six-year clinical trials at 14 leading research institutions across the country.
  116. [116]
    Senolytics target cellular senescence — but can they slow aging?
    Sep 2, 2024 · Senolytics have been found to dramatically increase lifespan in mice (by as much as 27%). And rodents treated with these drugs do not just live ...
  117. [117]
    Senolytic therapy shows subtle impact on age-related bone health in ...
    Feb 27, 2025 · An NIA-funded clinical trial investigating whether senolytics could improve bone health in older women had just subtle results.
  118. [118]
    A pilot study of senolytics to improve cognition and mobility in older ...
    Feb 25, 2025 · This single-arm study evaluates the feasibility, safety, and preliminary effects of two senolytic agents, Dasatinib and Quercetin (DQ), ...
  119. [119]
    The geroprotectors trametinib and rapamycin combine additively to ...
    May 28, 2025 · Combined treatment significantly increased lifespan compared to the individual drug treatments (log-rank test).
  120. [120]
    Sex-specific insights into drug-induced lifespan extension and ...
    May 19, 2025 · Here, we demonstrate that pharmacological lifespan extension significantly correlates with weight loss in male mice, particularly in studies ...Missing: review | Show results with:review
  121. [121]
    Human trials exploring anti-aging medicines: Cell Metabolism
    Jan 4, 2024 · Here, we summarize the current knowledge on eight promising drugs and natural compounds that have been tested in the clinic.
  122. [122]
    Harnessing Genetics to Extend Lifespan and Healthspan
    Mar 4, 2024 · This review presents relevant recent advances in genetics and cell biology that are shedding new light by untangling how subtle changes in ...
  123. [123]
    Genetic associations with human longevity are enriched for ... - NIH
    Aug 1, 2024 · We identified six genes whose burden of loss-of-function variants is significantly associated with reduced lifespan: TET2, ATM, BRCA2, CKMT1B, BRCA1 and ASXL1.
  124. [124]
    Epigenetic reprogramming as a key to reverse ageing and increase ...
    Epigenetic modifications are the primary drivers of the ageing process. Transcription factors can induce cellular age reversal though epigenetic reprogramming.
  125. [125]
    CRISPR–Cas9 screens reveal regulators of ageing in neural stem ...
    Oct 2, 2024 · Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol. Med. 4, 691–704 ...
  126. [126]
    The Impact of CRISPR-Cas9 on Age-related Disorders
    The CRISPR-Cas9 system has become a potent gene-editing tool capable of correcting gene-mediated age-related pathology, and therefore ameliorating or ...
  127. [127]
    Bridging expectations and science: a roadmap for the future of ...
    Jul 1, 2025 · This article proposes a roadmap outlining the critical milestones necessary to advance longevity interventions from research to clinical readiness.
  128. [128]
    Potential Clinical Implications of Senotherapies for Cardiovascular ...
    More than 30 clinical trials of senolytics, including phase 2 randomized, double-blinded, placebo-controlled trials, are already underway or planned based on ...
  129. [129]
    Senolytic Therapy to Modulate the Progression of Alzheimer's ...
    This initial open-label clinical trial pilots an intermittent senolytic combination therapy of dasatinib plus quercetin in five older adults with early-stage ...Special Articles · Methods · Discussion<|separator|>
  130. [130]
  131. [131]
    Senolytics: from pharmacological inhibitors to immunotherapies, a ...
    Feb 6, 2024 · In this review, we present the senolytic drugs as a promising way to treat age-related diseases but also their limitations during clinical development.
  132. [132]
    Targeted partial reprogramming of age-associated cell states ...
    Sep 11, 2024 · Partial reprogramming via OSK expression in aged and stressed cells improved both median (about 40%) and maximal (about 32%) life spans in LAKI ...<|separator|>
  133. [133]
    Inside the scientific quest to reverse human aging
    Mar 6, 2025 · Can reprogramming our genes make us young again? A breakthrough in longevity research may be nearing its first human trials.
  134. [134]
    The long and winding road of reprogramming-induced rejuvenation
    Mar 2, 2024 · Another study demonstrated that partial reprogramming with dox-inducible OSK factors can extend the remaining lifespan of 124-week-old wild-type ...
  135. [135]
  136. [136]
    Results of a Crowdfunded One-Year Human Rapamycin Trial
    Apr 14, 2025 · This trial relied largely on self-reporting and did not provide direct evidence that rapamycin use extends the lives of humans, and most of its ...
  137. [137]
    Rapamycin for longevity: the pros, the cons, and future perspectives
    Jun 20, 2025 · Rapamycin has recently gained significant attention for anti-aging therapy and seizure treatment via mTOR pathway inhibition.
  138. [138]
    Deep learning and generative artificial intelligence in ... - Aging-US
    This review examines how Deep Learning (DL) and Generative Artificial Intelligence (GenAI) are used in biomarker discovery, deep aging clock development.
  139. [139]
    Emerging uncertainty on the anti-aging potential of metformin
    A recent meta-analysis combined the results of 22 clinical trials using metformin as an adjuvant cancer therapy, including the MA.32 trial described previously.
  140. [140]
    Caloric restriction - ScienceDirect.com
    Lifelong caloric restriction (CR) may extend life by up to 50% in rodents, with progressively less impact the later in life it is started.
  141. [141]
    Rapamycin fed late in life extends lifespan in genetically ... - NIH
    In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis ...
  142. [142]
    Rapamycin, Not Metformin, Mirrors Dietary Restriction‐Driven ...
    Jun 18, 2025 · This study suggests that rapamycin and DR confer comparable lifespan extension across a broad range of vertebrates.
  143. [143]
    Biological resilience and aging: Activation of stress response ...
    Instead, the mechanism of lifespan extension in germline-disrupted animals is mediated by the activation of multiple signaling pathways that promote longevity ( ...
  144. [144]
    Caloric restriction improves health and survival of rhesus monkeys
    Jan 17, 2017 · Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman ...
  145. [145]
    Does Calorie Restriction in Primates Increase Lifespan? Revisiting ...
    If these results can be readily translated to humans, it would mean that no beneficial effect of calorie restriction on lifespan can be expected in normal- ...
  146. [146]
    Analysis of animal-to-human translation shows that only 5% of ... - NIH
    Jun 13, 2024 · The overall proportion of therapies progressing from animal studies was 50% to human studies, 40% to RCTs, and 5% to regulatory approval.
  147. [147]
    Targeting ageing with rapamycin and its derivatives in humans
    Rapamycin fed late in life extends lifespan in genetically heterogeneous mice ... extension of a randomized controlled trial. Neurol Clin Pract. 2018; 8:412 ...
  148. [148]
    Challenges and opportunities of translating animal research into ...
    Sep 19, 2024 · The identified challenges concerning translating animal research into human trials are summarized into six themes: lack of finance and human ...
  149. [149]
    Implausibility of radical life extension in humans in the twenty-first ...
    Oct 7, 2024 · Olshansky et al. propose that, without medical breakthroughs that slow aging, radical lifespan extension is implausible in this century.Missing: skepticism | Show results with:skepticism
  150. [150]
    Implausibility of radical life extension in humans in the twenty-first ...
    Oct 7, 2024 · Over the course of the twentieth century, human life expectancy at birth rose in high-income nations by approximately 30 years, largely driven ...Missing: scientific skepticism Hayflick
  151. [151]
    Despite medical advances, life expectancy gains are slowing
    Oct 7, 2024 · In 1990, Olshansky published a paper in Science that argued humans were approaching a ceiling for life expectancy of around 85 years of age and ...Missing: skepticism Hayflick
  152. [152]
    Cohort mortality forecasts indicate signs of deceleration in ... - PNAS
    Aug 25, 2025 · A wide range of forecasting approaches suggests a significant deceleration in the pace of cohort life expectancy improvements for currently ...Missing: plateauing | Show results with:plateauing
  153. [153]
    The Gompertz Law emerges naturally from the inter-dependencies ...
    Jan 12, 2024 · We provide a universal explanation for the emergence of Gompertzian mortality patterns using a systems approach to describe aging in complex organisms.
  154. [154]
    Poor Translatability of Biomedical Research Using Animals
    Mar 7, 2023 · The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades.
  155. [155]
    (PDF) Poor Translatability of Biomedical Research Using Animals
    Mar 8, 2023 · The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past ...
  156. [156]
    Limits to lifespan growth - Frontiers
    Recent estimations suggest a limit of the maximum human lifespan of around 125 years (1, 2). In contrast, others disagree with possible limits to lifespan ...<|separator|>
  157. [157]
    Does the human lifespan have a limit? - Nature
    Jan 19, 2022 · “Gompertz speculated that this was a law equivalent to Newton's law of gravity,” says Jay Olshansky, an epidemiologist and gerontologist at ...
  158. [158]
    How do we age? A decomposition of Gompertz law - ScienceDirect
    Gompertz's law does not accurately capture mortality patterns among children and young adults, where accidental deaths overshadow biological aging. Additionally ...
  159. [159]
    Life Expectancy Is Plateauing, Won't Reach 100, Researchers Say
    Sep 4, 2025 · “We forecast that those born in 1980 will not live to be 100 on average, and none of the cohorts in our study will reach this milestone,” said ...
  160. [160]
    Snake oil is giving longevity research a bad name - STAT News
    Sep 26, 2025 · The longevity field has made major progress in the past decade, but anti-aging hype is getting in the way.Missing: skepticism | Show results with:skepticism
  161. [161]
    The Science (and Pseudoscience) of Aging | Skeptical Inquirer
    So it's only natural that antiaging remedies abound. Sadly, most of them are just false hope, hype, and snake oil. The consequences of aging are not all bad: ...
  162. [162]
    What Dermatologists Really Think About Those Anti-Aging Products
    Dec 21, 2023 · Cosmetics companies are trying to wow consumers with clinical-sounding ingredients. Actual scientists aren't impressed.
  163. [163]
    Wrinkle Treatments and Other Anti-aging Products - FDA
    Feb 25, 2022 · FDA is concerned about drug claims made for products marketed as cosmetics, such as skin care products with anti-wrinkle or anti-aging claims.
  164. [164]
    Warning Letters Address Drug Claims Made for Products ... - FDA
    FDA issued Warning Letters to the following firms, citing drug claims associated with topical skin care, hair care, and eyelash/eyebrow preparations.Missing: issues | Show results with:issues
  165. [165]
    Health Fraud Product Database - FDA
    This list includes unapproved products that have been subject to FDA health fraud related violations. These products have been cited in warning letters.
  166. [166]
    An FDA Regulator's View of the Issues with the FDA in ... - Fight Aging!
    Jan 21, 2022 · There is no established regulatory path to approval for treatments that target aging. So at present biotech and pharma companies working on ...
  167. [167]
    Hurdles for FDA Approval of Anti-Aging Therapies
    Sep 17, 2024 · Given the FDA's stance on not defining aging as a disease, scientists do not have a regulatory pathway forward for the approval of their ...
  168. [168]
    [PDF] How to Identify Health Fraud Scams
    Marketers of fraudulent products will make sweeping promises, but not return your money. Health Fraud Scams Target Older Adults. Anti-aging scams:Despite claims ...
  169. [169]
    A Cost-Based Analysis of Anti-aging Products Across Four Major ...
    Oct 6, 2023 · We analyzed the unit cost of four anti-aging products from major online and physical retailers in the United States.
  170. [170]
  171. [171]
    The dark side of beauty: an in-depth analysis of the health hazards ...
    This review explores the toxicological impact of beauty and personal care products on human health, highlighting the dangers posed by various chemicals.
  172. [172]
    Nobel laureate alarmed by over-hyped longevity research - YouTube
    Mar 11, 2024 · Could we one day cheat death? Are we hurtling towards a time when science will be so advanced that aging can be prevented or halted in its ...
  173. [173]
    Rapamycin for longevity: opinion article - PMC - NIH
    The second reason is that there is rightful skepticism about any claims made about anti-aging drugs because thousands of anti-aging remedies have already failed ...Abstract · Figure 1 · Figure 3
  174. [174]
    Meet Ming the clam - the oldest animal in the world!
    Feb 11, 2020 · At 507 years of age Ming the clam broke the Guinness World Record as the oldest animal in the world. Collected off the coast of Iceland in 2006.
  175. [175]
    Eye lens radiocarbon reveals centuries of longevity in the Greenland ...
    Aug 12, 2016 · Radiocarbon dating of eye lens nuclei from 28 female Greenland sharks (81 to 502 cm in total length) revealed a life span of at least 272 years.Missing: evidence | Show results with:evidence
  176. [176]
    Greenland shark revealed to have longest life expectancy of all ...
    Aug 12, 2016 · The researchers find that the estimated life span of a fully grown Greenland shark female over five metres in length is at least 272 years.
  177. [177]
    Greenland sharks have massive genomes. Scientists think ... - CNN
    Dec 13, 2024 · Research published in 2016 determined the sharks are the longest-living vertebrates, likely living to be around 400 years old.
  178. [178]
    What is the longest-lived marine mammal?
    Jun 16, 2024 · According to scientists, this colossal year-round Arctic dweller may live 200-plus years. The bowhead's lifespan may be the second-longest of ...Missing: maximum | Show results with:maximum
  179. [179]
    Bowhead Whale | NOAA Fisheries
    However, new techniques allow for more precise estimation of bowhead whale age, and studies suggest they may live to be over 200 years old. Genes that allow for ...Missing: maximum | Show results with:maximum
  180. [180]
    Bowhead whale (Balaena mysticetus) longevity, ageing, and life ...
    The bowhead whale has been recorded as the longest-lived mammal thanks to one male estimated to be 211 years-old.
  181. [181]
    How Old Is the World's Oldest Turtle? 5 Turtles that Survived for ...
    Feb 3, 2025 · Harriet the Giant Galapagos Land Tortoise, 175 years. Why Do Tortoises Live So Long? DNA analysis from giant tortoises in the Galapagos ...
  182. [182]
    The longest living animals on Earth | Live Science
    Apr 5, 2024 · Saltwater crocodiles: 120+ years old ... If they survive to adulthood, saltwater crocodiles (Crocodylus porosus) normally live for over 70 years.Saltwater crocodile · Bowhead whale · Rougheye rockfish · Greenland sharkMissing: verified | Show results with:verified
  183. [183]
    Long-Lived Trees Are Not Immortal - PubMed
    Separating out the different effects of ageing on long-lived trees remains challenging. Herein current approaches used to explore senescence in millennial ...
  184. [184]
    How can some trees survive for thousands of years? | Britannica
    In addition, a study of bristlecone pine pollen found no significant increase in mutation rates with age, which is another factor associated with animal aging.
  185. [185]
    How the Ginkgo biloba achieves near-immortality | Science | AAAS
    Some forest giants, like the Ginkgo biloba, can live more than 3000 years. Now, in the most comprehensive plant aging study to date, researchers have revealed ...
  186. [186]
    Growing old while staying young: The unique mechanisms that defy ...
    Jan 26, 2024 · Although plants age like any other organisms, they have evolved to defy death for millennia and potentially forever.
  187. [187]
    Plants possess the formula for eternal life, but humans are unable to ...
    Mar 1, 2024 · The survival strategy of so-called clonal plants is to form ... quaking aspen, and is estimated to be between 14,000 and 40,000 years old.
  188. [188]
    Perennial Roots to Immortality, - PMC - PubMed Central - NIH
    In the plant kingdom, the maximum lifespans described for clonal and nonclonal plants vary by an order of magnitude, with 43,600 and 5,062 years for Lomatia ...
  189. [189]
    Longevity of clonal plants: why it matters and how to measure it - PMC
    Clonal plants are considered to be immortal and several extreme life spans reported seem to confirm this. Senescence, defined here as the apparent weathering or ...
  190. [190]
    The Role of Cytokinins and Gibberellins on Post-Harvest Longevity ...
    Cytokinins (CKs) and gibberellins (GAs) are considered to be ageing inhibitors; however, unfortunately, their content in the plant tissues decreases during the ...
  191. [191]
    Aging, stress, and senescence in plants: what can biological ...
    Feb 15, 2021 · Aging, stress, and senescence in plants are interconnected processes that determine longevity. We focus here on compiling and discussing our current knowledge.
  192. [192]
    Plant polyphenols: The secret to living longer and healthy aging?
    Oct 2, 2024 · Plant polyphenols show promise in combating aging, supporting mitochondrial health and reducing inflammation, potentially improving quality ...<|separator|>
  193. [193]
    Genetic mechanisms of aging in plants: What can we learn from them?
    The longest-living plant species may hold the keys to longevity in humans. · Plants have a leaky “Weismann barrier” between somatic and germinative tissues.
  194. [194]
    The central role of stem cells in determining plant longevity variation
    Feb 24, 2023 · Stem cells are the main source of plant longevity. Variation in plant longevity is highly dependent on the activity and fate identity of stem cells.
  195. [195]
    Do 'blue zones,' supposed havens of longevity, rest on shaky science?
    Nov 21, 2024 · Blue zones, supposed havens of longevity, have become a global brand. But skeptics think they rest on shaky science.
  196. [196]
    The secret of 'Blue Zones' where people reach 100? Fake data, says ...
    Sep 26, 2024 · The Blue Zones are really just a by-product of bad data, argues Newman, who has spent years debunking research about extremely elderly populations.Missing: refuted | Show results with:refuted
  197. [197]
    Ig Nobel Prize-winning research: Longevity claims may reflect “lousy ...
    Sep 17, 2024 · Newman found that many of these claims were likely due to errors or gaps in documentation, rather than true biological longevity. While ...
  198. [198]
    'The data on extreme human ageing is rotten from the inside out' – Ig ...
    Sep 13, 2024 · Saul Newman's research suggests that we're completely mistaken about how long humans live for.Missing: pseudoscience | Show results with:pseudoscience
  199. [199]
    The secret to a long life? Fraud and shoddy record keeping, says ...
    Sep 25, 2024 · New research out of the UK appears to debunk most instances of super centenarians, or extra-long lives, as fraud and bad record-keeping.
  200. [200]
    The Legal Issues: Anti-Aging Quackery: Human Growth Hormone ...
    Federal law states that distributing or administering human growth hormone for anti-aging or age-related problems is illegal.
  201. [201]
    Common Health Scams | Consumer Advice
    Anti-Aging Products​​ But here's what to know about HGH: The FDA says there's no clear evidence to support anti-aging claims for over-the-counter pills and ...
  202. [202]
    Consumer Alert on Regenerative Medicine Products Including Stem ...
    Jul 22, 2020 · None of these products have been approved to treat autism, macular degeneration, blindness, chronic pain, or fatigue. Contacting FDA. If you are ...Missing: debunked | Show results with:debunked
  203. [203]
    A Science-Based Review of the World's Best-Selling Book on Aging
    Sep 26, 2022 · Lifespan: Why We Age and Why We Don't Have To, written by Harvard scientist David A. Sinclair with assistance of journalist Matthew D. LaPlante.