What the Hallmarks of Aging Are and Which Ones You Can Actually Influence

What Are the Hallmarks of Aging?

The hallmarks of aging are a classification of the biological processes that change as organisms age and that appear to drive age-related decline. Carlos López-Otín and colleagues proposed the first list in Cell in 2013 to give the field a shared vocabulary (López-Otín et al., 2013). To qualify, a process should show up during normal aging, worsen aging when experimentally made worse, and slow aging when experimentally improved. Few candidates meet all three tests in every species, which is why the authors called the original list tentative.

This framework sits underneath the idea of geroscience, the argument that targeting the biology of aging could delay many chronic diseases together (Kennedy et al., 2014). For the outcome those mechanisms feed into, see what healthspan means and why it matters more than lifespan.

What Are the Twelve Hallmarks?

The 2013 paper listed nine hallmarks in three groups: causes of damage, the body's responses to damage, and the end results that show up as decline. The 2023 update kept those nine and added three: disabled macroautophagy, chronic inflammation, and dysbiosis, meaning a disturbed gut microbiome (López-Otín et al., 2023).

Several of these have their own guides on Protocol: senescent cells, epigenetic age, and NAD+ and mitochondrial function. The hallmarks interact, so damage in one area often feeds another. Treating the list as twelve independent targets misreads how the authors framed it.

How Strong Is the Evidence That You Can Change Them?

It varies a lot by hallmark, and it is much stronger in animals than in people. The clearest example is cellular senescence. Baker and colleagues (2016) used a genetic switch to clear p16Ink4a-positive cells from mice starting at one year of age. Treated mice lived longer than controls, and several organs showed less age-related deterioration. That is a proof of concept in mice, not a treatment available to people. For humans, the main randomized signal comes from calorie restriction. In the CALERIE trial, two years of sustained calorie restriction slowed the DunedinPACE pace-of-aging measure compared with controls, but did not significantly change two other epigenetic clocks, and the authors described the effects as small (Waziry et al., 2023).

Which Hallmarks Can You Actually Influence?

Realistically, you influence them indirectly, through habits that touch several hallmarks at once. This table is a hedged map of plausible links, not a promise. These are general associations from the wider research literature, and the strength of evidence differs for each row. The habits themselves have the most consistent human support: in two large US cohorts, five low-risk habits (not smoking, healthy weight, regular activity, moderate alcohol, better diet) were linked to many more years free of cancer, cardiovascular disease, and type 2 diabetes (Li et al., 2020).

For the fitness side of this picture, read why VO2 max predicts how long you will live.

What Is the Most Common Misconception?

That the hallmarks are a to-do list, with a supplement or protocol for each one. The framework describes where aging biology shows up, not which products work.

What Should You Do With This?

Use the framework to understand why basic habits matter, then put your effort where the human evidence is strongest.

Frequently Asked Questions