See below for Peter’s important point of view. How to solve this part of aging via lifestyle? Is it possible? Can I reduce the damage enough and increase the repair mechanisms enough to substantially delay this outcome? I’m working the angle that my body is smart and knows what to do if I give it the right signals plus help out with a bit of extra autophagy, and make sure I am not deficient for long in anything important.
“ Even disease-free, humans become increasingly fragile. Aging isn’t just a sum of diseases; it’s the progressive accumulation of irreversible damage leading to a linear decline of key functional indicators, such as IQ, VO2max, EGFR (kidney function), etc. A 90-year-old without disease is still functionally a disabled version of their younger self.”
I think that he is describing a damage theory of aging which I do not feel corresponds well with the facts. The major theories of aging among scientists are usually antagonistic pleiotropy (genes good for youths are bad for older people) and controlled death (death is evolutionarily advantageous). Neither of those theories associate the cause of death with any cellular damage.
Chromatin signaling through AP-1 leads to older genes being expressed which leads to worse health over time. This is more because of older gene expression being expressed due to various evolutionary reasons and mistakes, but they are fundamentally examples of changes in gene signaling. Some examples of this include how Gene expression leads to the end of neuroplasticity around 25, and how there there is reduced bdnf, desire to learn, klotho/creatine, stem cell repair, TERT, plus everything in between. It’s been discussed before here about the occurrence of self-starvation among seniors and the sudden signaled death of mothers in salmon and octopi(controlled death). There certainly are some components of damage in aging (Hayflick limit, extracellular damage, stem cells), but they probably are not the most serious issue at all.
In fact, I have seen that there are some AP-1 inhibitor drugs being researched like SR 11302 which could theoretically slow down older gene expression, but it has not gotten to the point where the progressive chromatin signaling has ever been reversed.
There seems to be a two track solution here. I don’t necessarily disagree with Peter, but if you want public support (which is critical for things like ITP funding, etc.) I think you really want to focus on healthspan.
If you just read through the comments (e.g. The NY Times recent article comments on their website) on the rapamycin story, you see most people seem to be against life extension (largely, I believe, because they equate it to more years of frailty and suffering).
The mistake that the average person makes is that he/she correlates increased lifespan with being sicker for a longer period of time at the end of life. The reality is that both lifespan and health span get better or worse at the same time.
Some aspects of how we humans work is not accounted for in this evaluation.
There are things that our body can not repair through “lifestyle”
Thymus
Elastin
Both of these things are critical for a longer healthy life span. There are probably other similar systems that I’m not aware of, that are life span and health span limiting, regardless of lifestyle.
There is hope for the Thymus but diet, supplements and exercise are not the answer. It requires a significant intervention, so no matter how you live your life, that won’t fix this problem.
Elastin - we stop making it when we enter puberty. This means, similar to the thymus, that no matter our lifestyle we will lose all our elastin. Elastin has a 70 year half life, this simple fact limits our lifespan to about 120 years.
Until I see a solution for elastin rejuvenation, the “dream” of living healthily beyond 100 is a pipe dream.
Those are simple facts that are overlooked by so many “eternal life” proponents that have not dug into what is currently not fixable in the human system. Hopefully some gene or other therapy will address elastin.
Kind of a fruitless argument. Lifespan and health span are overlapping bell curves that are tied together . Other than at the extremes, anything you do to move one curve will move the other.
if it was marketed as “age reversal” most people would be in favor IMO.
Marketed as living forever, people focus on being old and having elderly frailties and disease.
Heathspan will never catch on as it is too vague
I think that he is describing a damage theory of aging which I do not feel corresponds well with the facts.
Chromatin signaling through AP-1 leads to older genes being expressed which leads to worse health over time.
I’ve read some of his papers and I can say that he’s using damage in a broader sense than just chemical defacement of proteins and lipids, or overt DNA sequence changes.
The chromatin remodeling that occurs with aging would also constitute a form of damage (‘loss of epigenetic information’, etc).
I agree. Here is his quote modified a bit so we can focus on the problem instead of semantics
How to avoid this outcome or at least delay it for a long time?
“Even disease-free, humans become increasingly fragile. Aging isn’t just a sum of diseases; it’s [also] the progressive [non-disease driven…] linear decline of key functional indicators, such as IQ, VO2max, EGFR (kidney function), etc. A 90-year-old without disease is still functionally a disabled version of their younger self.”
I believe rapamycin plays a role here (immune functions). I also think starting to fight back before the functional indicators fall below some minimum threshold is critical.
There is a separation, but not in a good way, with medical practice currently. The average American has 16 years of multiple comorbidities before death is a figure I’ve heard discussed.
So getting to 60 and starting to be disabled, and dying at 76 is the typical American male’s outcome.
Medical care keeping people alive, at substantial cost, and with many of these individuals having very poor quality of life has pushed out lifespan beyond healthspan and probably will increase this pattern.
Well, then things aren’t looking too bad for my lineage. My father is 77 without any comorbidities. However he isn’t as spry as he was, so he hasn’t aged perfectly.
People often look at life expectancy averages the wrong way. Those averages include a lot of deaths at young ages. So, although the average life expectancy in the US is 75-78, if you make it to 60, you have a life expectancy of 82-85. A healthy 70 yo has a 50% chance of getting to 90.
True. Most importantly much of the improvement in life expectancy over say 200 years is as a result in a reduction of infant mortality which is not really Gompertz related.
