The hallmarks of aging are the biological changes scientists use to describe how and why the body ages — a shared shortlist of the processes that reliably show up as we get older. There are currently twelve of them, and together they are the closest thing science has to a map of aging. This guide walks through each one in plain English, explains why researchers group them the way they do, and — just as important — is honest about what the framework can't tell you.
If you're in your 40s, 50s, or 60s and trying to make sense of the longevity noise online, the hallmarks are a genuinely useful place to start. They are not a product, a protocol, or a promise. They're a way of thinking clearly about a subject that attracts a lot of hype.
What are the hallmarks of aging?
The hallmarks of aging are a set of biological processes that reliably change with age and appear to drive much of the decline we associate with getting older. The idea was introduced in 2013 by a group of aging researchers led by Carlos López-Otín, in a now-landmark paper in the journal Cell. They proposed nine hallmarks. In 2023, the same team updated the framework to twelve.
To qualify as a hallmark, a process has to pass three tests: it should appear during normal aging, making it worse should speed aging up, and — in laboratory models — acting on it should be able to slow, stop, or even reverse signs of aging in that system. That last test is where much of the excitement (and much of the overselling) in the longevity world comes from. It's worth holding onto the words 'in laboratory models.'
In one line: the hallmarks of aging are the twelve interconnected biological processes — from genomic instability and mitochondrial dysfunction to chronic inflammation — that scientists use as a shared map for how and why the body changes with age.
The 12 hallmarks of aging at a glance
Here is the full list, each in plain English, with the grouping the original researchers used to make sense of them.
| Hallmark | In plain English | Group |
|---|---|---|
| Genomic instability | DNA accumulates damage over time, and repair becomes less reliable. | Primary |
| Telomere attrition | The protective caps on the ends of chromosomes gradually shorten. | Primary |
| Epigenetic alterations | The 'switches' that turn genes on and off drift out of their youthful pattern. | Primary |
| Loss of proteostasis | Cells get worse at folding proteins correctly and clearing out damaged ones. | Primary |
| Disabled macroautophagy | The cell's internal recycling and cleanup system slows down. | Added 2023 |
| Deregulated nutrient-sensing | The pathways that read energy and food signals fall out of balance. | Antagonistic |
| Mitochondrial dysfunction | The cell's power plants become less efficient at producing energy. | Antagonistic |
| Cellular senescence | Damaged cells stop dividing but linger instead of clearing out. | Antagonistic |
| Stem cell exhaustion | The body's pool of repair-and-replacement cells runs low. | Integrative |
| Altered intercellular communication | The signals cells send each other get noisier and more inflammatory. | Integrative |
| Chronic inflammation | Low-grade, persistent inflammation builds up over the years ('inflammaging'). | Added 2023 |
| Dysbiosis | The balance of the gut microbiome shifts with age. | Added 2023 |
The nine original hallmarks came from the 2013 paper; disabled macroautophagy, chronic inflammation, and dysbiosis were the three added in the 2023 update as the evidence matured.
Why do scientists group them? The three categories, simply
Twelve items is a lot to hold in your head, so the original framework sorted the first nine into three tiers. It's the single most useful thing to understand about the hallmarks.
Primary hallmarks are the sources of damage — the things that genuinely go wrong at the molecular level, such as DNA damage and shortening telomeres. Antagonistic hallmarks are the body's responses to that damage. In small doses they're protective; sustained over decades, they start to cause problems of their own — cellular senescence is the classic example. Integrative hallmarks are the end results, the tier where all of that upstream trouble finally shows up as the visible decline of tissues and organs.
A rough analogy: the primary hallmarks are the leak in the roof, the antagonistic ones are the buckets and towels you put out to cope, and the integrative ones are the water stain that eventually spreads across the ceiling. It's imperfect — the real biology is a web, not a straight line — but it captures why researchers see the hallmarks as a cascade rather than a checklist.
What was added in 2023 — and why it matters
The 2023 update didn't overturn the original nine; it extended them. Three processes had earned enough evidence to join the list: disabled macroautophagy (the cleanup system faltering), chronic inflammation (the slow, background 'inflammaging' that tracks with age), and dysbiosis (shifts in the gut microbiome). The bigger point of the update was that the hallmarks are deeply interconnected — pull on one thread and several others move. That interconnectedness is why no single hallmark is 'the cause' of aging, and why the search for one magic fix keeps coming up short.
Where does cellular energy fit in?
Several hallmarks touch the same theme: how cells make and manage energy. Mitochondrial dysfunction, deregulated nutrient-sensing, and altered communication all sit close to metabolism. One molecule that runs through this territory is NAD+, a coenzyme central to energy metabolism and a required partner for enzymes involved in DNA repair and cellular housekeeping. Research shows that tissue and cellular NAD+ levels gradually decline with age across multiple organisms, including humans, which is part of why NAD+ has become such a focus in aging biology.
This is exactly the kind of area where it pays to separate the science from the sales pitch — which is what we do in why NAD+ matters →, and, more broadly, in our honest look at whether you can reverse aging →. The short version: NAD+ decline is real and well-studied, but 'a molecule declines with age' is not the same as 'topping it up fixes aging.' The evidence in people is still developing.
What the hallmarks can — and can't — tell you
Used well, the hallmarks are a fantastic mental model. They explain why aging is a whole-body process, why interventions studied in mice don't automatically work in humans, and why 'cellular health' is more than a marketing phrase. They give you a vocabulary to ask better questions.
But they have limits worth stating plainly. The hallmarks are a research framework, not a diagnosis and not a to-do list — you can't 'check off' a hallmark. They describe biology in cells and model organisms; translating them into things a person can actually do is early, uneven science. And they are not a shopping list: no supplement, routine, or device has been shown to reverse the hallmarks of aging in humans. Anyone selling you that certainty is ahead of the evidence.
So, to be direct about what the hallmarks framework will not do: it won't hand you a reversal you can buy, it won't predict your personal healthspan, and it won't replace the basics — sleep, movement, nutrition, not smoking, and regular care from your own clinician — that still do the heavy lifting.
What this means for a daily routine in midlife
For most women moving through their 40s, 50s, and 60s, the honest takeaway is calming rather than urgent. The hallmarks reinforce the unglamorous fundamentals: the things that support healthy aging are mostly the things you already know, done consistently. A supplement, if you choose to take one, is a small and optional part of that picture — not the center of it.
That's the lane CELLSHE stays in. We build a clean, premium daily routine around cellular wellness rather than promises. Our Cellular Trio → pairs NMN, NAD+, and resveratrol as one simple daily ritual — NMN 500 supports cellular energy production and NAD+ biosynthesis* — designed to be consistent, transparent, and easy to keep. If you want to see how those three ingredients fit together, we break it down in the longevity stack, explained →. It's one considered choice among the fundamentals, not a shortcut around them — so it's worth reading which longevity supplements are actually worth it → before you buy anything.
Frequently asked questions
What are the hallmarks of aging?
They're twelve interconnected biological processes — such as genomic instability, mitochondrial dysfunction, and chronic inflammation — that reliably change with age and are used by scientists as a shared framework for understanding how the body ages.
How many hallmarks of aging are there?
There are currently twelve. Nine were proposed in 2013, and three more — disabled macroautophagy, chronic inflammation, and dysbiosis — were added in the 2023 update.
Who came up with the hallmarks of aging?
A team of aging researchers led by Carlos López-Otín first proposed them in the journal Cell in 2013, and published the expanded twelve-hallmark version in 2023.
Can the hallmarks of aging be reversed?
In laboratory models, researchers can influence some hallmarks, and that's an active area of study. In people, this remains early science — and no supplement, routine, or product has been shown to reverse aging. Be skeptical of any such claim.
Do supplements target the hallmarks of aging?
No supplement is proven to 'fix' a hallmark. Some nutrients are studied for their role in cellular energy and metabolism, and may support a healthy-aging routine*, but a supplement is one optional part of the fundamentals — not a replacement for them. Talk to your clinician about what's right for you.
References
- López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. (2013). The hallmarks of aging. Cell. PMID: 23746838. pubmed.ncbi.nlm.nih.gov/23746838
- López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. (2023). Hallmarks of aging: An expanding universe. Cell. PMID: 36599349. pubmed.ncbi.nlm.nih.gov/36599349
- Covarrubias AJ, Perrone R, Grozio A, Verdin E. (2021). NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology. PMID: 33353981. pubmed.ncbi.nlm.nih.gov/33353981
- National Institute on Aging (NIH). Understanding the biology of aging. nia.nih.gov
