Biological aging

Organismal senescence is the aging of whole organisms. Actuarial senescence can be defined as an increase in mortality or a decrease in fecundity with age. The Gompertz–Makeham law of mortality says that the age-dependent component of the mortality rate increases exponentially with age.

Aging is characterized by the declining ability to respond to stress, increased homeostatic imbalance, and increased risk of aging-associated diseases, including cancer and heart disease. Aging has been defined as "a progressive deterioration of physiological function, an intrinsic age-related process of loss of viability and increase in vulnerability."

In 2013, a group of scientists defined nine hallmarks of aging that are common between organisms with emphasis on mammals:

In a decadal update, three hallmarks have been added, totaling 12 proposed hallmarks:

The environment induces damage at various levels, e.g., damage to DNA, and damage to tissues and cells by oxygen radicals (widely known as free radicals), and some of this damage is not repaired and thus accumulates with time. Cloning from somatic cells rather than germ cells may begin life with a higher initial load of damage. Dolly the sheep died young from a contagious lung disease, but data on an entire population of cloned individuals would be necessary to measure mortality rates and quantify aging.

The evolutionary theorist George Williams wrote, "It is remarkable that after a seemingly miraculous feat of morphogenesis, a complex metazoan should be unable to perform the much simpler task of merely maintaining what is already formed."

Different speeds with which mortality increases with age correspond to different maximum life span among species. For example, a mouse is elderly at 3 years, a human is elderly at 80 years, and ginkgo trees show little effect of age even at 667 years.

Almost all organisms senesce, including bacteria which have asymmetries between "mother" and "daughter" cells upon cell division, with the mother cell experiencing aging, while the daughter is rejuvenated. There is negligible senescence in some groups, such as the genus Hydra. Planarian flatworms have "apparently limitless telomere regenerative capacity fueled by a population of highly proliferative adult stem cells." These planarians are not biologically immortal, but rather their death rate slowly increases with age. Organisms that are thought to be biologically immortal would, in one instance, be Turritopsis dohrnii, also known as the "immortal jellyfish", due to its ability to revert to its youth when it undergoes stress during adulthood. The reproductive system is observed to remain intact, and even the gonads of Turritopsis dohrnii exist.

Some species exhibit "negative senescence", in which reproduction capability increases or is stable, and mortality falls with age, resulting from the advantages of increased body size during aging.

More than 300 different theories have been posited to explain the nature (mechanisms) and causes (reasons for natural emergence or factors) of aging. Good theories would both explain past observations and predict the results of future experiments. Some of the theories may complement each other, overlap, contradict, or may not preclude various other theories.

Theories of aging fall into two broad categories: evolutionary theories of aging and mechanistic theories of aging. Evolutionary theories of aging primarily explain why aging happens, but do not concern themselves with the molecular mechanism(s) that drive the process. All evolutionary theories of aging rest on the basic mechanisms that the force of natural selection declines with age. Mechanistic theories of aging can be divided into theories that propose aging is programmed, and damage accumulation theories, i.e. those that propose aging to be caused by specific molecular changes occurring over time.

The aging process can be explained with different theories. These are evolutionary theories, molecular theories, system theories and cellular theories. The evolutionary theory of ageing was first proposed in the late 1940s and can be explained briefly by the accumulation of mutations (evolution of ageing), disposable soma and antagonistic pleiotropy hypothesis. The molecular theories of ageing include phenomena such as gene regulation (gene expression), codon restriction, error catastrophe, somatic mutation, accumulation of genetic material (DNA) damage (DNA damage theory of aging) and dysdifferentiation. The system theories include the immunologic approach to ageing, rate-of-living and the alterations in neuroendocrinal control mechanisms. (See homeostasis). Cellular theory of ageing can be categorized as telomere theory, free radical theory (free-radical theory of aging) and apoptosis. The stem cell theory of aging is also a sub-category of cellular theories.

One theory was proposed by George C. Williams and involves antagonistic pleiotropy. A single gene may affect multiple traits. Some traits that increase fitness early in life may also have negative effects later in life. But, because many more individuals are alive at young ages than at old ages, even small positive effects early can be strongly selected for, and large negative effects later may be very weakly selected against. …

If different individuals age at different rates, then fecundity, mortality, and functional capacity might be better predicted by biomarkers than by chronological age. However, graying of hair, face aging, skin wrinkles, and other common changes seen with aging are not better indicators of future functionality than chronological age. Biogerontologists have continued efforts to find and validate biomarkers of aging, but success thus far has been limited.

Levels of CD4 and CD8 memory T cells and naive T cells have been used to give good predictions of the expected lifespan of middle-aged mice.

There is increasing interest in epigenetic clocks as biomarkers of aging, based on their ability to predict human chronological age. Many epigenetic aging clocks are based on DNA methylation, but alternative epigenetic clocks are also starting to emerge, e.g. based on nucleosome positioning derived from cell-free DNA. Basic blood biochemistry and cell counts can also be used to accurately predict the chronological age. It is also possible to predict the human chronological age using transcriptomic aging clocks.

There is research and development of further biomarkers, detection systems, and software systems to measure the biological age of different tissues or systems or overall. For example, a deep learning (DL) software using anatomic magnetic resonance images estimated brain age with relatively high accuracy, including detecting early signs of Alzheimer's disease and varying neuroanatomical patterns of neurological aging, and a DL tool was reported as to calculate a person's inflammatory age based on patterns of systemic age-related inflammation.

Aging clocks have been used to evaluate the impacts of interventions on humans, including combination therapies. Employing aging clocks to identify and evaluate longevity interventions represents a fundamental goal in aging biology research. However, achieving this goal requires overcoming numerous challenges and implementing additional validation steps.

Several genetic components of aging have been identified using model organisms, ranging from the simple budding yeast Saccharomyces cerevisiae to worms such as Caenorhabditis elegans and fruit flies (Drosophila melanogaster). Study of these organisms has revealed the presence of at least two conserved aging pathways.

Gene expression is imperfectly controlled, and random fluctuations in the expression levels of many genes may contribute to the aging process, as suggested by a study of such genes in yeast. Individual cells, which are genetically identical, nonetheless can have substantially different responses to outside stimuli, and markedly different lifespans, indicating the epigenetic factors play an important role in gene expression and aging as well as genetic factors. There is research into epigenetics of aging.

The ability to repair DNA double-strand breaks declines with aging in mice and humans.

A set of rare hereditary (genetics) disorders, each called progeria, has been known for some time. Sufferers exhibit symptoms resembling accelerated aging, including wrinkled skin. The cause of Hutchinson–Gilford progeria syndrome was reported in the journal Nature in May 2003. This report suggests that DNA damage, not oxidative stress, is the cause of this form of accelerated aging.

A study indicates that aging may shift activity toward short genes or shorter transcript length and that this can be countered by interventions.