Why We Age: Damage, Programmed, or Both?
Wading through recent papers about the limit of lifespan.
Life happens at a predictable rate for nearly all 8 billion of us on Earth.
We call it reaching developmental milestones in childhood — baby teeth erupt, crawling, walking, permanent teeth coming in, puberty hitting — growth happens at a consistent, programmed rate around the world.
In middle age, we no longer call it reaching a milestone when the need for reading glasses happens, hair turns gray, menopause, blood pressure creeps up, etc.
What controls that rate?
Fundamental questions of aging and lifespan extension include: What controls and drives aging? Why is there a hard limit on lifespan?
When looking at animals, maximum lifespan is consistent for animals in the same species and conditions (e.g. horses live 25-30 years, field mice live 1-2 years). We wouldn’t expect to find a 100-year-old horse, but it’s reasonable for a tortoise. Every animal has consistent developmental milestones, and a fairly consistent maximum lifespan and reproductive span. A mouse 2 years, a naked mole rat 30 years.
On a practical level, understanding the rate of aging, the constraints, and whether we can turn back the clock are important to me as I contemplate retirement planning.
There are a lot of smart people trying to figure this out. I’m going to present some of the competing frameworks here. Please forgive any errors in my understanding of this and any missteps in my thinking.
Programmed Aging vs. Damage Accumulation:
Overarching theories on aging fall into two camps: 1
Damage accumulation: Random cellular damage gradually accumulates until repair systems can't keep up, causing aging in each organ and tissue. Within this, the question is whether the inability to repair is due to epigenetic control being damaged.
Programmed aging: Other theories look at aging as a program that controls gene expression through development, adulthood, and then actually causes programmed aging.
Hallmarks of Aging: Damage happens and accumulates
In 2013, researchers put together a list of what they considered the ‘hallmarks of aging’. This was updated in 2023 (article in Cell) with additional systemic hallmarks that drive aging. The hallmarks include cellular senescence, telomere shortening, chronic inflammation, mitochondrial dysfunction, genetic damage, etc. — all the tangible changes that are seen at a cellular level in aging.
These are all independent causes, and each hallmark needs a separate fix (although some interrelate). The different types of damage are fundamentally causing aging. Evolutionary biologists talk about there not being any selection pressure to live past our reproductive span.
This still leaves me with the question: Why do all these things happen together around the same time? Aging happens in bursts; it isn’t linear.
Information theory of aging: Epigenetic control that gets damaged
In 2019, David Sinclair published a book called Lifespan: Why We Age and Why We Don’t Have To. In it, he lays out his information theory of aging in which he argues that epigenetic changes are like software that becomes corrupted over time — like a scratched-up CD. In a 2023 article in Nature, Dr. Sinclair updates this idea of being able to reverse the epigenetic changes and reset cells to a younger age.
This puts aging under epigenetic control - like a program, but the program gets randomly damaged to cause aging. Fixing it is just a matter of restoring the epigenetic information back to what it was at a prior time point. Cleaning the scratches on the CD.
This leaves me with the question: Why was the epigenetic information lost? I understand the software vs. hardware analogy, but I just don’t quite buy it. Especially since aging isn’t a linear progression.
Programmed gene expression: Centralized control sets lifespan
Other researchers argue that there’s an overarching program that controls gene expression throughout the body that sets the pace for development through to old age. This program then controls embryonic and early development, shifts to a different profile for maintaining health during the reproductive years, and then shifts again to a late period that either allows or actually causes the destruction of normal functions.
A recent article argues that the brain is the rate-limiting organ. It regulates the rest of the physiological systems in the body, with perhaps the hypothalamus as the central controlling pacemaker for both aging and lifespan.
Questions that aren’t answered:
To me, the question is whether there’s a centralized, overarching control that allows the breakdown of the body at a certain age, or whether damage just builds up randomly.
It seems like damage causes epigenetic changes, and that epigenetic changes cause damage. Partially reprogramming cells with Yamanaka factors (Yang, 2023) can extend cellular lifespan. Is this because it is restoring information or that it is improving multiple hallmarks?
Are the ‘hallmarks’ of aging the cause or the consequence? Does accumulated damage drive aging, or does aging (perhaps pre-programmed) drive the accumulation of damage?
The overarching idea of a program that controls development and aging for an organism makes sense to me. Developmental stages, reproductive years — all of that is experientially true. What I don’t quite have my mind wrapped around is the idea that part of the program is a deliberate stopping of repair mechanisms, such that we go downhill towards death.
Why is this even important?
A recent preprint from researchers at the Weizmann Institute of Science showed statistically what I think is something that most people instinctively know: Lifestyle and dietary interventions for longevity only extend lifespan by about a year. Yeah, the study was a bunch of statistics, averages, and the use of the word stochastic. It may not be true for each individual. However, it’s consistent with what larger studies show.
Is it worthwhile to spend extensive time and money on ‘longevity’ if the payoff is living to 83 instead of 82? (Yes, I know that healthspan is important, too, but that’s not what I’m pondering here.)
What do we know for sure?
I’ve put a lot of questions in this article, without a lot of answers. Sometimes, taking a look at what is known can help clarify what still needs to be figured out. Here are some “knowns” that may be helpful to think about:
Not linear:
Aging happens in bursts rather than at a steady linear rate. Think about the changes from infancy to age three or four, the momentous changes in puberty, that feeling in your early 40s that you’re no longer what you were a few years ago, and then the jump towards being ‘old’ that happens in the early 60s. If you want to read the research on it, this paper by Shen et al. (2024) lays it out in excruciating detail.
Organs age at different rates:
A recent study in Nature aging looked at how organ-specific aging predicts disease onset and mortality. Using proteomic data from the UK Biobank, the researchers developed 10 organ-specific aging algorithms that demonstrated that organs age at different rates within individuals. Brain aging had the strongest link to mortality.
Similar animals have vastly different lifespans:
Even among mammals of the same size, there can be almost 10-fold differences in lifespan (such as mice vs. naked mole rats). Then there’s the hydra, which is biologically immortal.
Immortal cells:
Certain cell lines and tissue cultures in labs can be maintained for decades. They don’t age like cells in the body do. An example is a mouse fibroblast cell line, 3T3, that researchers have been using since 1962. Why do those same tissues or cell types get old and die in the body? (If you want an interesting book on the HeLa cell line that has been used since the 50s, check out The Immortal Life of Henrietta Lacks. It’s a good read on a lot of levels.)
Where does this leave me?
The idea that inflammaging can be tackled with anti-inflammatories, that DNA damage can be avoided if we eat clean and avoid toxins, that mitochondrial dysfunction can be avoided with the right supplement, or that we can get a whole body glow up with some young plasma — all of that is tangible, understandable, and feels like taking the right steps. (OK, maybe not the young plasma. I’m not going to do that.)
Extending healthspan is worthwhile, and that is what addressing the hallmarks of aging or even reprogramming cells in a specific tissue will do. I’m going to keep on with this pursuit. I want to be as healthy as possible in middle age and don’t want to be debilitated in old age.
The reality, though, is that none of these ‘longevity lifehacks’ is likely to move the needle more than a few years in the end.
I’m ok with that, to some extent. But I am unsatisfied with not having the answers to why we age, what controls the timing, and what imposes the hard limit on lifespan.
I can’t help but wonder what happens when the control system - centralized or decentralized - is understood well enough to be manipulated. I’m planning and saving for retirement, with goals and financial analysis based on both a realistic lifespan and then stretching that a few years (a fudge factor, so that I don’t outlive my retirement money).
The societal implications of manipulating lifespan are huge, but on a personal level, I’m disquieted and don’t know how to balance the uncertainty with action.
Suggested reading:
https://www.frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2025.1695510/full
https://www.biorxiv.org/content/10.64898/2025.12.22.695887v1 - maximum lifespan mechanistic model of aging
https://en.nagoya-u.ac.jp/news/articles/is-aging-an-act-of-genetic-sabotage-for-the-greater-good-scientists-find-a-gene-that-turns-off-food-detection-after-reproduction/
https://www.nature.com/articles/s43587-025-01016-8
https://yurideigin.medium.com/death-becomes-her-or-why-aging-is-an-epigenetic-program-c55a32fd8c74
https://www.cell.com/cell/fulltext/S0092-8674(22)01570-7?
https://www.mdpi.com/2073-4425/12/5/611
https://pmc.ncbi.nlm.nih.gov/articles/PMC6555444/
https://pmc.ncbi.nlm.nih.gov/articles/PMC6413751/
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=5368732
Love this! Well written!
In my experience living in mould is like throwing a biological accelerant onto every mechanism discussed in this article.
It simultaneously increases damage accumulation and disrupts epigenetic control. Mycotoxins drive chronic inflammation, oxidative stress, mitochondrial dysfunction, immune dysregulation, hormone disruption, and impaired DNA repair. That’s basically a checklist of the hallmarks of aging happening all at once, and happening early.
What’s fascinating is how mould exposure makes aging feel “non-linear.” People often don’t decline slowly. They hit sudden collapses in energy, cognition, skin quality, hormonal stability, and resilience. That mirrors your point about aging happening in bursts rather than a smooth slope.
It also challenges the idea that aging is purely programmed. When the environment is toxic enough, the system is forced into accelerated entropy. The “program” may exist, but mould corrupts the execution layer. It scrambles the epigenetic software and damages the hardware simultaneously.
In that sense, mould is a real-world experiment in accelerated aging:
• Faster epigenetic drift
• Faster mitochondrial decay
• Faster inflammatory aging
• Faster neurological aging
And unlike abstract longevity theory, it shows how environment can override biology.
For people who have lived in mould, aging isn’t theoretical. It’s observable, visceral, and often reversible once exposure stops. That alone suggests that aging isn’t just a fixed clock, but a dynamic system highly sensitive to environmental toxicity.
Which makes clean air, clean buildings, and low-toxin environments not lifestyle luxuries, but core longevity medicine.
Rhonda Patrick introduced me to the longevity notion. It is not in our collective dialog, quite the opposite (yolo mentality). So first we have to overcome this societal nihilism. Then ...have a purpose for living, physical and mental stimulation to keep us active and learning.