Aging refers to the progressive decline of physiological functions over time [1]. Although aging is common across many species, it is not a universal phenomenon [2]. Some organisms show little or no physiological deterioration with age, while others, including humans, experience significant decline in fitness. This variation raises key questions that this review addresses: Why do some species “age” while others do not? Why do mammals, particularly humans, experience progressive health decline? And if natural selection improves survival and reproduction, why does aging evolve at all? This review focuses on applying evolutionary theories of aging to the context of human geriatric circumstances.

In 1891, August Weismann proposed that aging eliminates worn-out members from a population [3]. Later, Fisher and Haldane argued that aging arises because natural selection has a weaker impact on survival and reproduction at old age [4][5]. Hamilton, Medawar, Rose, and Williams extended these ideas, emphasizing that extrinsic mortality weakens selection against late-acting deleterious mutations [6][7]. By the mid-20th century, evolutionary biologists formulated a theory of aging based on population genetics: the force of natural selection declines with age, allowing deleterious mutations that manifest later in life to accumulate [1][8]. Thus, aging is not an adaptive benefit to species but a non-adaptive consequence of declining selection efficacy with age [8][9].

Patterns of aging differ across species. Some show clear senescence, others negligible senescence (little or no decline of fitness), and a few exhibit negative senescence (improved performance with age) [10]. For example, the aquatic cnidarian Hydra displays negligible senescence under laboratory conditions [11]. About 95% of angiosperms show no clear signs of aging, and many trees live for centuries [12]. Aging tends to evolve in species with a clear germline-soma distinction and age structure [13]. Thus, aging is not a universal phenomenon [2].

The evolutionary theory of aging is founded on three fundamental mechanisms: mutation accumulation, antagonistic pleiotropy, and the disposable soma theory [8][14]. Together, these mechanisms provide complementary explanation for why senescence evolves. Mutation accumulation and antagonistic pleiotropy describe how genetic variants with late-life costs can persist in populations. The disposable soma-theory adds a resource-allocation logic: because natural selection prioritizes early reproduction over indefinite somatic maintenance, organisms are evolutionarily constrained from investing fully in repair, allowing damage to accumulate with age. A summary of these three mechanisms and their relevance to human geriatric research is provided below (see Table 1).

Table 1. Summary of evolutionary mechanisms of aging.

Recent comparative studies across species have quantified the relationship between extrinsic mortality and senescence. Species with higher extrinsic mortality (e.g., small fish, rodents) exhibit rapid senescence with mortality rates exceeding 50%, while species with low extrinsic mortality (e.g., elephants) exhibit slower aging [20][21]. Bats provide a particularly striking case: despite their small body size, many bat species have very low extrinsic mortality due to flight and nocturnal habits, and they exhibit exceptional longevity—some live up to 40 years with minimal age-related decline. Comparative genomics has revealed that long-lived bats have evolved enhanced DNA repair pathways and reduced inflammatory signaling, consistent with the disposable-soma theory’s prediction that reduced extrinsic mortality favors investment in somatic maintenance [21].

While comparative studies reveal correlations, CRISPR-Cas9 gene editing has enabled direct, causal tests of genes known to mediate trade-offs between early fitness and late-life decline. For example, CRISPR-mediated knockdown of IGF-1R in mice extends lifespan, supporting antagonistic pleiotropy [22]. These experiments provide stronger causal evidence than observational studies alone. Cross-species data relating patterns of senescence to extrinsic mortality rates is shown in Table 2 below.

Table 2. Cross-species evidence linking extrinsic mortality to senescence.

Although aging is mostly associated with deterioration of physiological functions, laboratory environments can alter their expression. Dietary restriction (reducing food intake without malnutrition) extends lifespan and delays age-related diseases in many vertebrates and invertebrates [8][23]. In rhesus monkeys, caloric restriction reduces insulin and triglyceride levels, limiting diabetes and cardiovascular diseases [24]. Protein restriction, rather than overall caloric reduction, may drive many of these benefits in rodents and primates [24]. Translation to humans remains uncertain, and current evidence does not justify recommending protein restriction for longevity without further research.

Trade-offs between reproduction and longevity are common; bats that produce more offspring have shorter lifespans than those that produce fewer offspring [21]. Social insects such as termites and bees also show unusual aging patterns: queens live longer than workers despite their high fertility [25]. These patterns likely arise from protection from extrinsic mortality and social structures rather than from an absence of aging. Species such as naked mole rats and Hydra are often described as exhibiting negligible senescence, but this does not mean they are exempt from aging; rather, their aging patterns are unusually slow or non-progressive under specific conditions.

Ongoing research aims to extend human lifespan by studying slow-aging species. Naked mole rats exhibit negligible senescence and cancer resistance [10]. Planarian flatworms possess pluripotent stem cells capable of regenerating aged tissues [11]. Although no species is truly immortal, these models reveal mechanisms that slow aging. In humans, clinical interventions include the use of metformin (originally for diabetes), which improves cognitive function and slows brain aging in male monkeys [26][27]. Senotherapy, which targets senescent cells, has also proven effective in improving conditions such as osteoporosis and reducing chronic inflammation [28][29].

Recent discoveries in molecular biology have provided insight into cellular mechanisms that govern aging, with telomerase regulation emerging as a central player [30]. Telomeres—protective DNA repeats at chromosome ends—shorten with each cell division due to the endreplication problem. When telomeres become critically short, cells enter senescence or apoptosis, contributing to tissue dysfunction, inflammation, and agerelated disease [30]. Telomerase, the enzyme that elongates telomeres, is tightly regulated in somatic cells but active in germ cells, stem cells, and many cancer cells. Ecologically, species with lower extrinsic mortality (e.g., birds, bats) tend to have longer telomeres and higher telomerase activity, supporting an evolutionary link between environment and molecular aging mechanisms [31].

The table below compares the patterns of aging among few species and their relevance to humans (see Table 3).

Table 3. Comparing aging patterns across species.

The translational implications of evolutionary aging theories are vast. Gene-editing technologies such as CRISPR-Cas9 offer potential therapeutic strategies to delay human aging [32]. For example, editing pro-aging genes (e.g., PCSK9) for cardiovascular health, or targeting senescent cells via CRISPR-based knockout of BCL-2 family members, is being explored in preclinical models [33]. However, ethical considerations and off-target effects remain barriers. Future research should therefore prioritize:

Extensive human cohort research relating evolutionary hypotheses to clinical results CRISPR-based screening to identify geroprotective gene variantsClinical trials of senolytics and metformin in diverse populations

It should be noted however, that converting the interdisciplinary integration of molecular biology, ecology, and clinical gerontology will be essential to translating evolutionary theories into safe and effective human therapies.

The evolution of aging is a complex subject in evolutionary biology and varies across different taxa. Natural selection acts more strongly on early-life traits, leading to fitness decline with age in humans. Rather than viewing aging as inevitable, research should focus on ecological and genetic factors that shape aging patterns. Clinical interventions are promising but may present side effects; hence, their benefits must outweigh risks. Nevertheless, extrinsic factors such as accidents and infections remain difficult to control and can cut lives short before old age. A pragmatic goal is to reduce the burden of age-related diseases and extend health span.

I would like to thank Dr. Peer, for reviewing this paper.