So, having talked to a number of people in longevity biotech, I’m skeptical as to whether view (1) i.e. Sinclair’s ‘information theory of aging’ which posits epigenetic aging is the master regulator for the other hallmarks is accurate, and that cellular reprogramming alone is sufficient to slow aging. I think the information theory of aging is good PR for the field, but I don’t think it’s entirely correct.
Still, the next 5 years of research will provide more clarity as to the relationship between epigenetic alterations and the other hallmarks of aging. I hope (1) is true although from the data I’ve seen and people I’ve spoken to behind the scenes, I don’t think it’s likely that cellular reprogramming alone will be enough.
I think the hallmarks develop to some extent independently, even though there is some level of cross-talk between them, and will have to be individually addressed.
Very curious to hear a bit more about why you are skeptical about epigenetics and information theory of aging as the primary cause. But I completely agree that it’s not the only cause!
“Being sufficient to slow aging” is a pretty low bar, I have virtually no doubt that reprogramming will slow aging (it already has been done experimentally with mice).
I don’t see a lot of evidence for the information aging theory in the literature, and most geroscientists don’t seem to think that epigenetics is the master regulator of the other hallmarks. This isn’t to say it’s not true, just that there’s insufficient evidence at this point.
Sinclair discusses all of the hallmarks, but focuses on epigenetics as the most important—which is incidentally the one he studies. Bear in mind as an academic this is something are incetivised to do—to tell a narrative that fits their research agenda, to attract funding.
Looking at the field as a whole, there is consensus about the hallmarks but not so much consensus about the information aging theory, and in fact I don’t know of any other major geroscience researchers who have endorsed the information theory of aging. It’s too early to say that he’s incorrect, but the theory seems unlikely from my reading.
Methylation increases with age and predicts biological age
Methylation affects protein synthesis in a semi-random way
Those points mean that epigenetics at least partially causes all hallmarks dependent on protein synthesis (loss of proteostasis, intercellular communication, etc). Meaning that epigenetics is at least partially upstream of at least a few hallmarks.
Not sure what being correct about information theory of aging would exactly mean or what other evidence to expect. Intuitively it feels that our efforts should focus upstream and that there are more low hanging fruits in epigenetics than in most of the other hallmarks.
That seems plausible! The only thing I’ll say is that from what I’ve heard, epigenetic reprogramming in vivo may be particularly challenging in many tissues in the body. Therefore, I suspect mTOR inhibitors and senolytics may be lower hanging fruit for anti-aging therapies approved first.
Hi Alexey,
So, having talked to a number of people in longevity biotech, I’m skeptical as to whether view (1) i.e. Sinclair’s ‘information theory of aging’ which posits epigenetic aging is the master regulator for the other hallmarks is accurate, and that cellular reprogramming alone is sufficient to slow aging. I think the information theory of aging is good PR for the field, but I don’t think it’s entirely correct.
Still, the next 5 years of research will provide more clarity as to the relationship between epigenetic alterations and the other hallmarks of aging. I hope (1) is true although from the data I’ve seen and people I’ve spoken to behind the scenes, I don’t think it’s likely that cellular reprogramming alone will be enough.
I think the hallmarks develop to some extent independently, even though there is some level of cross-talk between them, and will have to be individually addressed.
Very curious to hear a bit more about why you are skeptical about epigenetics and information theory of aging as the primary cause. But I completely agree that it’s not the only cause!
“Being sufficient to slow aging” is a pretty low bar, I have virtually no doubt that reprogramming will slow aging (it already has been done experimentally with mice).
I don’t see a lot of evidence for the information aging theory in the literature, and most geroscientists don’t seem to think that epigenetics is the master regulator of the other hallmarks. This isn’t to say it’s not true, just that there’s insufficient evidence at this point.
Sinclair discusses all of the hallmarks, but focuses on epigenetics as the most important—which is incidentally the one he studies. Bear in mind as an academic this is something are incetivised to do—to tell a narrative that fits their research agenda, to attract funding.
Looking at the field as a whole, there is consensus about the hallmarks but not so much consensus about the information aging theory, and in fact I don’t know of any other major geroscience researchers who have endorsed the information theory of aging. It’s too early to say that he’s incorrect, but the theory seems unlikely from my reading.
Interesting, thanks! My thinking is that:
Methylation increases with age and predicts biological age
Methylation affects protein synthesis in a semi-random way
Those points mean that epigenetics at least partially causes all hallmarks dependent on protein synthesis (loss of proteostasis, intercellular communication, etc). Meaning that epigenetics is at least partially upstream of at least a few hallmarks.
Not sure what being correct about information theory of aging would exactly mean or what other evidence to expect. Intuitively it feels that our efforts should focus upstream and that there are more low hanging fruits in epigenetics than in most of the other hallmarks.
That seems plausible! The only thing I’ll say is that from what I’ve heard, epigenetic reprogramming in vivo may be particularly challenging in many tissues in the body. Therefore, I suspect mTOR inhibitors and senolytics may be lower hanging fruit for anti-aging therapies approved first.