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 is honest about what the framework cannot tell you.
If you are 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 are 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 (PMID 36599349).
To qualify as a hallmark, a process has to pass three tests:
- It appears during normal aging. The process shows up as part of getting older.
- Making it worse speeds aging up. Pushing on it accelerates the signs of aging.
- Acting on it can slow or reverse those signs, in laboratory models. This last test is where much of the excitement, and much of the overselling, in the longevity world comes from. Hold 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 12 hallmarks of aging, one by one
Now each hallmark in a little more detail, grouped the way the original researchers did.
1. Genomic instability
DNA picks up damage throughout life, and the systems that repair it become less reliable. Over decades, those unrepaired errors accumulate. It is a primary hallmark, a genuine source of damage.
2. Telomere attrition
Telomeres are the protective caps on the ends of your chromosomes, a bit like the plastic tips on shoelaces. Each time a cell divides they get a little shorter, and eventually the cell can no longer divide safely. A primary hallmark.
3. Epigenetic alterations
Your DNA sequence stays largely the same, but the chemical switches that decide which genes are on or off drift away from their youthful pattern. That changes how cells behave. A primary hallmark.
4. Loss of proteostasis
Cells work hard to fold proteins into the right shape and to clear out damaged ones. With age that quality control slips, and misfolded proteins build up. A primary hallmark.
5. Disabled macroautophagy
Autophagy is the cell's recycling and cleanup crew, breaking down worn-out parts so they can be reused. When it slows, cellular junk lingers. This was added in the 2023 update.
6. Deregulated nutrient-sensing
Cells constantly read signals about available energy and food. With age these sensing pathways fall out of balance. An antagonistic hallmark: helpful in the short term, costly when sustained for decades.
7. Mitochondrial dysfunction
Mitochondria are the tiny power plants inside your cells. As they become less efficient, cells have less clean energy to work with. An antagonistic hallmark.
8. Cellular senescence
Damaged cells sometimes stop dividing but refuse to clear out, lingering and sending inflammatory signals to their neighbors. In small numbers this is protective; in large numbers it causes trouble. The classic antagonistic hallmark.
9. Stem cell exhaustion
Stem cells are the body's repair-and-replacement pool. As that pool runs low, tissues heal and renew more slowly. An integrative hallmark, where upstream damage finally shows up.
10. Altered intercellular communication
Cells constantly talk to each other with chemical signals. With age that conversation gets noisier and more inflammatory. An integrative hallmark.
11. Chronic inflammation
Low-grade inflammation quietly builds in the background over years, a process nicknamed 'inflammaging.' This was added in the 2023 update.
12. Dysbiosis
The gut microbiome, the community of microbes living in your digestive tract, shifts in composition with age. This was added in the 2023 update.
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 is 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 are 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 is imperfect, the real biology is a web and 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 did not 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 it.
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. The popular story that NAD+ simply falls with age is being revised. A 2026 whole-blood study across seven separate groups of people found levels did not clearly fall with age (PMID 42135539), while in older men with sarcopenia across three ethnicities, muscle NAD+ and the enzymes that produce it were measurably reduced versus age-matched healthy controls (PMID 31862890).
So the useful question is less about running a deficit and more about giving the body what it uses to keep making NAD+. That is why research attention has moved to precursors, the compounds shown to support NAD+ biosynthesis.
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: even where a molecule changes with age, 'a molecule changes 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 do not 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:
- They are a research framework, not a diagnosis and not a to-do list. You cannot '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.
- 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 will not hand you a reversal you can buy, it will not predict your personal healthspan, and it will not 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 considered layer on top of those fundamentals, a routine you keep, not a replacement for them.
That is the lane CELLSHE stays in. We build a clean, premium daily routine around cellular wellness rather than promises. Our Cellular Trio → ($109, or $99 monthly) pairs NMN 500, NAD+, and Resveratrol 600 as one simple daily ritual, with NMN 500 to support 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 is one considered choice among the fundamentals, not a shortcut around them, so it is worth seeing where a clean, evidence-informed routine fits in which longevity supplements are actually worth it →. Curious where you stand? Take the free Cellular Age Check →.
If you want to see how these hallmarks map onto everyday habits after 40, our field guide walks through the practical levers section by section.
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 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
- Whole-blood NAD+ concentration across seven independent cohorts (2026). PMID: 42135539. pubmed.ncbi.nlm.nih.gov/42135539
- Migliavacca E, et al. (2019). Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities. Nature Communications. PMID: 31862890. pubmed.ncbi.nlm.nih.gov/31862890
- National Institute on Aging (NIH). Understanding the biology of aging. nia.nih.gov
