Highlights
- Researchers from Germany argue that the rate of aging is dependent on stochastic (or random) error accumulation, rather than a specific rate of aging
- This error accumulates slower in species where there are a lot of error correction mechanisms in their cells
- This explains why these species have longer lives than other species
- Could we extend our lifespans by boosting our DNA error correction mechanisms?
Different species age at different speeds
An alternate theory proposes that aging is a programmed process. In that it is simply a natural continuation of the development process of an organism from childhood to maturity when they reproduce and pass on their genes. But then this maturation process just continues further into aging. Further support towards this programmatic aging has come from the recent advent and popularity of epigenetic clocks. Simply put these epigenetic clocks show that certain epigenetic marks, methyl group added onto DNA, change with age. Importantly, this change is dependent mostly on age and partly on the overall health of the organism. This has given rise to the idea of biological age versus chronological age: an exciting concept because it implies that we can perhaps do something about our biological age even though we cannot slow down time. In the last decade or so since the advent of the first epigenetic clock, this has given rise to a whole industry of experts and companies purveying diet, exercise, supplements, and drugs that claim to slow down a person’s biological age.
Does better DNA repair equal longer lifespan?
Fortunately, nature has done an important experiment for us that provides key insights into how edging might be slowed. We see that species that have very highly tuned DNA repair mechanisms tend to live longer than other species that do not. This gives us the idea that it regardless of how DNA damage accumulates over time, be it by accumulation of random mutations or as part of a clock-like mechanism, if we can efficiently repair the damage that accumulate over time, it should lead to a longer lifespan.
Indeed, some experiments are giving us reason for hope that DNA repair will translate to a longer life. First, in the nematode C. Elegans reproductive cells, DNA are repaired very carefully, compared to the rest of the cells of the body. This happens because a DNA repair protein complex called DREAM is activated in the reproductive cells but not in the rest of the body of C. Elegans. So, if we can use a drug to inhibit this repressor complex in all cells, we should be able to turn up the DNA repair process and enhance DNA repair. In fact, when this was done in mice with accelerated aging phenotype, their DNA repair was improved, and it prevented loss of eyesight. Beyond just genetic changes, epigenetic changes can also be reversed using the so-called Yamanaka factors. an idea that has seen a lot of excitement around it with many ultra-wealthy folks investing in companies trying to do just that.
Can we fine tune our DNA repair mechanisms to live longer?
With this insight, it is natural to ask: Can we boost our DNA repair mechanisms? And what, if anything, can we do about it? While much of the technology to reverse genetic and epigenetic damage still remain in the research domain, evidence suggests there are a few things we can do a do about it. For one, we know that prolonged fasting followed by refeeding can induce epigenetic reprogramming which lowers biological age. This is exciting because it suggests that at least transiently we can slow down or reverse some of the age-associated damage. Indeed, there are also some supplements that may help fine tune flagging DNA repair mechanisms or slow down epigenetic changes. Look for more on that coming soon.
Meyer, D.H. et. al. Aging by the clock and yet without a program https://doi.org/10.1038/s43587-025-00975-2
Link to a read-only version kindly shared by the first author https://x.com/Meyer_DH/status/1968802053280444434
Lopez-Otin, C. et.al., Hallmarks of aging: An expanding universe https://doi.org/10.1016/j.cell.2022.11.001
Kagan, A. et. al. Somatic mutation rates scale with lifespan across mammals.https://pmc.ncbi.nlm.nih.gov/articles/PMC9021023/
Bujarrabal-Dueso, et. al., The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities. https://doi.org/10.1038/s41594-023-00942-8