The hallmarks of aging :
what they explain and what they don't.

You get the definition in plain words, the three versions of 2013, 2023 and 2025 at a glance, and the state of what has actually been shown in humans. By the end you will know why training is the broadest lever in this model, why a telomere test says little, and why “acts on the hallmarks of aging” is not a quality feature of a product.

TL;DR

The hallmarks of aging are a map of aging research : first nine, since 2023 twelve, since 2025 fourteen processes that increase with age and, in animal experiments, accelerate or slow aging. They are not proof of what causes aging in humans, and they are not a treatment guide. In humans, none of the agents that specifically target a hallmark has been shown to benefit the lifespan or independence of healthy people. According to current evidence, training has the broadest effect : it changes markers of several hallmarks at once and, in a large randomised trial in sedentary older adults, made major mobility disability less frequent. Lower mortality has not yet been established in randomised trials, not even for training.

1. What exactly the hallmarks of aging are

In 2013, Carlos López-Otín, Guido Kroemer and colleagues compiled in the journal Cell which biological changes characterise aging at the level of cells and tissues. They named nine such features, in English hallmarks. The paper became one of the most cited texts in aging research.

A process only made it onto the list if it met three conditions :

The authors themselves write that the hallmarks meet these conditions to varying degrees, the third one least of all. And the experiments on which conditions two and three rest come mainly from worms, flies and mice. In humans, the evidence consists mostly of associations with age, genetic findings and rare syndromes of premature aging.

In 2023, the same group expanded the list to 12, in 2025 to 14. The hallmarks are arranged in three groups : primary hallmarks, where damage arises ; antagonistic ones, that is, the body's responses to this damage, which protect at first and cause harm themselves in excess ; and integrative ones, in which the whole shows up as a loss of function.

For context : the version with 12 hallmarks dates from 2023 ; in 2013 there were nine. And the hallmark altered intercellular communication refers to communication between cells, not within a cell.

2. What the model is not

Not proof of cause in humans. That a process shortens or extends life in mice does not show that it drives aging in humans. An animal can also live longer because a treatment prevents one specific fatal disease, without aging as a whole slowing down (Keshavarz 2023).

Not a list of separate construction sites. The hallmarks are closely interlinked. Improving cellular cleanup also improves, in experiments, mitochondria, inflammation and genome stability. The authors themselves therefore describe the hallmarks as “different entry points” for influencing biological aging in experiments, not as separate pathways (Kroemer 2025).

Not a measuring instrument. Most hallmarks are difficult or impossible to measure in a standardised way in humans. For cellular breakdown (autophagy) there is no standard method outside the body. Telomere length in blood cells varies widely between people of the same age, and its decline does not predict loss of physical capacity in older adults (Kroemer 2025).

Not undisputed. Critics consider the model a useful overview but not an explanation : the selection is said to be partly arbitrary, the ranking of causes unresolved, and how concrete age-related diseases arise from the interplay remains open (Gems and de Magalhães 2021).

Not a seal of quality. Kroemer and colleagues themselves note in 2025 that many venture capitalists and biotech companies display the wheel of hallmarks while claiming to address one, several or all hallmarks at once. They do not question the value of the model as a framework for thinking. The wheel describes the biology. Whether a product achieves anything measurable in humans, it does not describe.

This article is for information in the context of lifestyle coaching. It is not medical advice, not a diagnosis and not a recommendation for any individual case. Substances and amounts mentioned come from the cited studies and are not a recommendation to take them. Prescription drugs belong in a doctor's hands. Felix Baier is neither a physician nor a German-licensed Heilpraktiker ; StoaVita sells no dietary supplements.

We placed nine interventions side by side. Only one passed a large randomised trial on function.

The wheel describes the biology ; the decisive question is what has been shown in humans. From training and calorie restriction to senolytics, rapamycin, metformin, NAD precursors, spermidine and urolithin A, the overview separates three things that tend to merge in advertising copy : a changed marker, a benefit on function or disease, and a benefit on lifespan. The pattern is clear, and even for training, two caveats remain.

Which question to ask of any product that claims to act on a hallmark, why two of three epigenetic clocks showed no difference under calorie restriction, what to do and what not to do, where StoaVita comes in, and where the model reaches its limits : that is the second part, along with the poster that puts the whole wheel on one page.

Poster · client area

All 14 hallmarks on one page

The wheel with the three groups and the additions since 2023 and 2025, sharp and complete after signing in to the client area.

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