The Hallmarks of Aging: A Framework, Not a Treatment Map

What the framework is

The "hallmarks of aging" are a list of shared biological features that researchers see in aging cells and tissues. The idea was set out in a 2013 review in the journal Cell by López-Otín and colleagues, which named nine "tentative" hallmarks seen across organisms, with special emphasis on mammals: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication. [1] A 2023 update in the same journal proposed twelve. [2] This page is education only. It describes a way of organizing research and makes no claim that any product or therapy acts on a hallmark in people.

Evidence labels follow how we label evidence in longevity research.

The twelve hallmarks, in plain words

The 2023 update lists genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation and dysbiosis. [2] The three added since 2013 are disabled macroautophagy, chronic inflammation and dysbiosis (an imbalance of the body's microbes). [2]

The three tests for a hallmark

The 2023 authors say a hallmark must meet three premises: it appears with age; making it worse experimentally speeds up aging; and there is an opportunity to slow, stop or reverse aging by acting on it with therapy. [2] Note that the third premise is a criterion for inclusion, not a finding that such therapies work in people. In the paper's own wording, the hallmarks are interconnected with one another and with newly proposed "hallmarks of health." [2]

What the framework is not

• Not a treatment map. The framework organizes biology. It does not show that targeting any one hallmark extends healthy life in humans. In the 2013 review the authors named, as a major challenge, working out how the candidate hallmarks connect and how much each contributes to aging. [1]
• Not a checklist for a clinic. A product sold to "fix" a hallmark is making a claim that needs its own human evidence. Label: marketing claim unless trials show a clinical outcome.
• Not settled. The list changed between 2013 and 2023 and the 2013 hallmarks were called "tentative." [1]
• Not independent of its authors' interests. The 2023 paper's disclosures list authors with company roles or stock tied to telomere testing and to senescence-targeting therapies. [2] This does not make the framework wrong, but it is worth knowing.

How researchers use it

Researchers use hallmarks to design experiments and to group findings. Early human trials of therapies aimed at basic aging processes are framed around age-related diseases, geriatric syndromes or resilience to stress, not around the hallmarks themselves. [3] Most hallmark evidence comes from cells and animals; see aging in animals vs humans.

For a general overview of the biology, read what is aging.