The official retirement age in many countries is between the ages 60 and 65. Workers are generally expected to live another 15 years or so, on average for a lifespan of roughly 80 years. But what if the expected lifespan were doubled, to around 160 years. Obviously retirement age would have to be raised significantly, to between 120 and 130 years, to prevent governments and pension funds from being bankrupted by long-lived retirees.
One Way the Human Lifespan Might be Doubled
We have all read about the combining of rapamycin-like drugs with metformin, a treatment for diabetes. These drugs seem to extend lifespan in worms and rats, but the benefit is unproven for humans. For mice, the life extension benefit is estimated to be an additional 25%, on average.
But a new study looking at analogues of the grape-derived chemical resveratrol, suggests that the door to an even greater extension of lifespan may be opening.
Restoring Senile Cells to Full Activity
The accumulation of senile cells in tissues is an unfortunate but expected consequence of aging. Senile cells do not reproduce, they do not perform the normal functions of cells for their tissue type, and they tend to spew out all types of toxic and destructive chemicals into their environment. They are implicated in Alzheimer’s disease and many other degenerative diseases of aging.
But here is the shocker: Resveratrol analogues appear to have the potential to restore senile cells [human fibroblasts] to normal function, with longer telomeres like younger cells, and the ability to reproduce themselves like younger cells can do.
While decreases in senescence biomarkers may be beneficial in alleviating some of the detrimental effects of senescent cells, it is the loss of proliferative capacity of senescent cell populations that is likely to lead to stem cell exhaustion and loss of tissue function/frailty with increasing age . We therefore also assessed cell proliferation and re-entry into the proliferative cell cycle. Initially, using live cell imaging of senescent NHDF cells treated with resveratrol for up to 92 h, we found that some cells within this population showed clear evidence of mitosis within a little as 17.5 h after treatment (Additional file 4: Figure S2). We therefore assessed whether senescent populations of three different fibroblasts lines (NHDF, MRC5 and HF043) could undergo mitosis following treatment with the novel compounds. Remarkably, treatment with even very low doses (5 μM) of the resveralogues led to significant increases (up to 0.6 population doublings) in total cell numbers over only 24 h of drug exposure, while vehicle-only controls remained proliferation-arrested (Fig. 5a). Increases in cell number strongly suggest that a significant proportion of cells in the non-cycling senescent population have been induced to re-enter the mitotic cell cycle.
… We found that cells treated with resveratrol or any of the novel resveralogues had telomeres that were 1.3–2.4 times longer than vehicle-only controls, compared with younger cells at PD25, which showed telomeres 2.6 times longer than untreated senescent cells (Fig. 5c). __ https://bmccellbiol.biomedcentral.com/articles/10.1186/s12860-017-0147-7
The researchers treated senescent human fibroblasts with a range of novel resveratrol analogues, and discovered that the fibroblasts stopped behaving as senescent cells and began behaving in multiple ways as younger cells capable of normal secretory patterns and capable of proliferation like younger cells.
Reading the full research study is an eye-opener, particularly when comparing the new findings with more conventional viewpoints of resveratrol action on human cells.
Accumulation of Senile Cells is One of the Chief Problems of Aging
Senile cells behave like little cluster bombs in aging tissue, releasing inflammatory cytokines that cause degenerative changes, cancer, and tissue destruction. In the famous SENS approach to anti-aging, one of the key treatments for aging is to remove these destructive senescent cells.
But resveratrol and some of its analogues tested in the research described above, seem to rescue and rejuvenate the senescent cells, rather than to kill and remove them, as SENS aims to do.
Many Questions Remain
I would not recommend trying to take out a one hundred year loan on a new house — it simply wouldn’t do, not unless Barack Obama was restored as US president when I wasn’t looking. 😉
But if the research above is replicated on multiple senescent cell types, you may wish to invest in a vineyard or two, if for no other reason than to develop your very own signature wine.
But seriously, if some relatively non-toxic method for thoroughly rejuvenating senescent cells of all human cell types could be found, it could represent a gateway to significant human life extension.
Resveratrol (and possibly Quercetin) May be Useful
Back in 2006, I recommended the consideration of Quercetin and Resveratrol in one’s experimental life extension routine. More research has been done since then, and it is possible that taking both phytochemicals together may boost resveratrol levels and the anti-senescent effect as well.
The main proven effect of taking large quantities of nutritional supplements is the production of very expensive urine. This fact has not change substantially over the past decades, but the research on resveratrol and its analogues discussed above gives reason to hope for at least a small breakthrough.
Perhaps expecting a doubling of lifespan and the necessary change in retirement age from 60 to 120, is too optimistic. But it is possible that in just a few years or decades, a lot more people will be voicing the complaint: “If I’d known I was going to live so long, I’d have taken a lot better care of myself!”
I did 5 days of Fisetin about a month ago and am doing the Quercitin/Tocotrienol protocol that LEF came up with about a year ago. I’ve noticed very minimal improvement but improvement none the less (I am 55 and had a slight bit of upper, not lower, back pain that completely went away). I suspect owing to the nature of my regimens, both supplements (NR/NAD+, AMPK, CoQ10/PQQ, and Resveratrol) and fitness (2 day split bodybuilding – 4 days per week and either swimming or hiking 3-4 times per week) that I have relatively few senescent cells to begin with.
The nice thing about all of this is the growing number of things that I can try on my own for life extension. The fact that my options for self-experimentation are growing makes it easier for me to “do my own thing” and avoid listening to the odious leftist politics that is driving me mad these days. I just need to get my system integration work going and I will be fine.
Right. Having access to a wide variety of potent supplements is a very good thing for the person who does his research. In fact, all kinds of medical knowledge should be democratised, not just life extension knowledge and expertise. (We’re going to need “bigger” brains)
The SENS people seem dedicated to obliterating senescent cells and ridding the body of them. Fair enough. But perhaps some senescent cells can be rejuvenated, becoming stem cells. The research on resveratrol analogues is intriguing in that regard, and needs replication and extension to many other cell types.
I read an interesting paper on invivo cellular reprogramming that made the argument that a certain level of senescent cells is necessary to provide a feedback signal to induce a certain level of cellular reprogramming for self-repair. This argument made sense to me. However, I still considered the senolytics to be worth trying because they are NOT 100% effective. Rather, they purge somewhere between 25% to 50% of senescent cells. If the paper i read is correct, that amount of senolytic efficacy might actually be more optimal than if it really did purge nearly 100% of the senescent cells.
The paper in question:
Thanks for the link. There are many layers of knowledge here, and we have barely scratched the surface.