The Health Improving Effects of Aspirin Depend on Autophagy
Many groups are attempting to develop calorie restriction mimetic drugs that produce benefits to health - and slow the progression of aging - by triggering some fraction of the stress response mechanisms engaged by the practice of calorie restriction. The most notable such mechanism is autophagy, a collection of cellular housekeeping processes that recycle damaged proteins and structures in the cell. Greater efficiency or activation of autophagy is a feature of a great many interventions known to slow aging in laboratory species.
Based on existing data, we should not expect any of these therapies to move the needle all that far on human life span, however. We have the example of calorie restriction, for which the health effects are fairly well known in human subjects. We also have aspirin, which is a calorie restriction mimetic, and is the subject of many very large human studies. Neither does all that much for life span in the grand scheme of things; a few years here, a few years there. We simply cannot expect novel calorie restriction mimetics to do more than modestly improve health and modestly reduce mortality, given this wealth of existing data that establishes the bounds of the possible for this approach to the treatment of aging.
Autophagy-mediated metabolic effects of aspirin
Aspirin is one of the oldest molecules to be used as a chemically defined entity for the treatment of human disease. Indeed, salicylate and its derivatives contained in plant extracts have been used since Mesopotamian times. As true for many other pharmaceutical agents, the effects of aspirin have been determined empirically to include anti-inflammatory, analgesic, and thrombosis-preventive effects before a molecular mode of action would have been postulated
Here, we investigated the metabolic effects of aspirin on the extracellular (plasma) and intracellular metabolome in mice by comparing them with those elicited by fasting. We and others have previously demonstrated that fasting or other caloric restriction mimetics than aspirin (such as spermidine and resveratrol) induce a broad deacetylation of multiple proteins involved in the regulation or execution of autophagy. We show that aspirin induces metabolic changes that are commensurate with the alterations produced by nutrient starvation, that it can indeed cause protein deacetylation in circulating white blood cells, that it inhibits EP300 but also other protein acetyltransferases, and that it mediates its positive metabolic effects through the induction of autophagy.
Indeed, the capacity of aspirin to reduce dietary adiposity, diabetes, and hepatosteatosis, as well as to enhance the efficacy of immunogenic chemotherapeutics, was lost in two distinct genetic mouse models of autophagy deficiency, as well as upon knockdown of Atg5 autophagy gene in cancer cells, respectively. Hence, the health-improving effects of aspirin depend on autophagy.
Ive also read that sildafenil/viagra increase lifespan.
Hi there! Happy New Year - Officially. Offtopic, Just a 2 cents. I just did a longevity stretching test upon a graphic (download to see image):
''https://www.cell.com/molecular-cell/pdf/S1097-2765(18)30642-7.pdf'' (check, Figure 3A).
When I stretchted that age 'arrow' of 100 years, I made it go to 640 years (by using paint tool and making that Arrow reach 6 centuries to the right). The first three girls (toddler/baby, young child girl and adult) are exactly the same (up to 20 years old young adult woman/just after puberty to become adult), then that is where it changes the 'slowing/plateauing of aging' that phase from '20-100' years old where things plateau and slow down and is why we can live to 100. The red women/girls (the bottom arrow) age faster and the death happens at roughly 75 years old (we can see that this is accelerated aging); the red icon women become nearly an Elder/old senior at Alraedy 65-70 years old (when they should reach Elder/senior age at like 80-95 years old). The blue icon girls/women (top arrow) age slower, we can see that the last woman is an Elder at like 80 years old and she still goes for '20 more' and is RIP/dies at 100 years old. So that is 20 More years or lifespan, that 80-100 last slice.
Between you and me (and the lamp-post on the other side of the street), everyone would take an extra 20, because that is nearly a new lease on life/ok not 30 years..but 20 is 20, not unsubtantial lifespan (that's 20% of a 100 year lifespan, thus not nothing). ''we'll take it''. Ok from the images, it is clear that old blue icon woman at 80 years old is suffereing/decriptiing of health and I could understand that someone would not want to be 20 years crippled from 80 to 100 years old. (Yet we do see octagenarians (80), nonagenarians (90) who 'function' enough and some can even do exercise, ride a bike..and don't necessarily have the crooked posture and a walking cane of that blue icon 80 year old senior woman).
OK, so what does the 600+ year old 'arrow' show? I shows this:
That 40 year old blue icon woman (top arrow, that looks at her cell phone), is now 'pushed back/way ahead in time'/post-poned; so now on the 600y Arrow she is 'spot on/arrives straight' on the 100 years old 'RIP' tomb icon.
As such, she would be - like a 40 years old (biologically/epigenetically) - AT - 100 years old (chronologically). Ok, the next one is the 60 year old women blue icon with a short dress, where does she fall in the future? She falls smacdab on the big 280 - yep, 280 Years old (nearly 300).
Now what about that 'last one', the aged grand-ma 80 years blue icon with a cane..drumm rolll...
460. (!)
And that RIP tomb...well, obviously, now falls on, 640, years old.
I know you are thinking...wuttttt?? Impossible right? (well, clams/sharks live 500 why impossible)
This graphic I updated could be quite close I think, because it showing 'moribidity compression' and extension 'of old age phase/period'', now what if we 'extrapolate it to Many centuries...we see exactly what I just told you.
In résumé:
- From your 40 years birthday - You will spend 60 (more) real years - as a 40 year old (epi/biologically/body), until you reach 100 years old anniversary (chronologically/in real time).
- From 100 years old to 280 years old, you will spend 180 years old as a middle-aged person, about roughly 50...around the age 180 years old (anniversary), you will be 50 years old 'biologically/body'. The Next 100 years, to reach 280, you will now be 60 bio years old
at - 280 years.
- And now for the Really Long part...from 280 to 460 years old (another 180), you will age to a biological 80 year old body (around 400 years old you will be 70 or so bio).
- The Final Stretch: 460 to 640 years old (180 more, last one), your body will be 100 years old at 640 years old (aroud 550, you will be 90 years old bio).
Ain't that a thing'...now I can already see/hear people scream: ''Whatttt? I will be an Elder FOREVER....ughhh pain for like ever'', yes, it does look like that, we have to remember/think of 'what it is to 'become someone of 100 years old'...but Stretch It over - 6 centurise..and you realize why, you will spend a very long time (4 centuries/400 years!) as an 'old person' - if you do live to 640 years like a clam. I can already see/read/hear people say: ''Never, I prefer die at 100 than spend 400 years as a decripting person..who wants to spend 400 year..decripting this long?''...I think that is valid point...
But I would say, we don't know yet, that if we can make epigenetic reprogramming we might make a 60 year old, a 90 year old, a 290 year old or 640 years old - BACK - to 40 years old biologically... but that remains to be seen. Which would mean we could stay 40 forever...like that ...but if we Do Age...but slow down Dramatically the process - to reach 640 year...
then..what I just said above Will Happen, because you will spend a very long time as a 40 year old (up to 100 years old)..and then from your 50 all the way to 90 years old biologically...you will 'stretch time' - until reach 640 years that have passed.
Kind of like dracular/vampires that supposedly live (in the literattrue) 4 5 centuries long, ...this extrapolation could be correct (if we do age for 600 years) because clams/sharks...are 'stretched' like that in time; as such a 500 year old Clam/greenlandshark...is old, will show lots of aging/decripit (have you seen a giant clam or gian greenland Shark of 400 years - it shows)...etc....thus, humans won't differ on that point and it will show that they are much older like Centuries Older. But overall their appearance will be like any grand-ma/grand-pa but Stretched Over Time/Centuries Time. Also, I am not sure but it is possible that humans that live 500some years may suffer 'gigantism'...because you will be 'so big/have such a long growth' over centuries...the best analogy is red Pine Trees/baobabs/cypress, huge trees that measure what 50 meter tall...they were never this big when Young...they Grew Up for Centuries into these giants/measuring so high...because they Had the Time to Grow (centuries) into these 'giants'.
Now with humans, when I look at clams (these clams don't become huge...but a bit bigger yes after centuries, while greenland sharks can reach 30 feet long after centuries...so they grow big), so it means, humans may 'Grown' to very high height, possibly like peoeple with acromegaly/gigantism (basketball players, Wrestling warrriors..who measure 7 or 8 feet tall..we might reach 10 feet tall after 300 years; let us remember that the pineal gland will produce all this growth hormones 'for growth' over all these years...so yes, that is a lot of growing up in height). With that you are supposed to 'stop growing' around 20 years old or so/maximal size...as we can see on the Arrow figure..the last woman is smaller and she has lost height (that is due to bone mineral density loss with age); but I am not sure that a 80 year old woman - who lived 80 birthdays/anniversaries and as a 80 year old biological body...will be the exact same height as a woman who is 80 years old biologically..but lived to the age of 640 years/ 640 anniversaries. Because that 640 year old woman (with an 80 year old biological body) has had a Lot of time to 'accumulate bone density'..and sure she would lose bone mineral density from 400 to 640 years of time passing.
So she could be either very smmalll...(no more bones) or she could be Huge Tall with lots of bone mineral deposited in her bones (like 9 feet tall). Normally, she should just not grow at all and only shrink - like it happens normally on that age arrow. Because we think that the Elder phase is with osteoporosis, sarcopenia, frailty and bone mineal loss...but we don't know how it is over centuries the same thing...normally..it would be 'Stretched/post-poned'..so that bone mineral density loss (from 60 to 80 years old biologically) would be stretched so long over time and thus she would become small height/crooked back (osteoporosis) veryyyyy slowlyl..like losing bone density/losing '5 inches of height over what...2+ centuries (400-640y)?...
I know this does not look very favorable...like who wants to be 'old' for centuries (if our biological reversal of aging is not possible to make us 'be 40 biologically again all the time'; but instead it can make us be 40 for let's say 200 years...and then yes, you become 50 biologically..and so forth until you hit 600 years chrono-realtime and your body is 100 years old biologically)...I guess we will have to see.
@Reason Hello Reason!
And the year review on longevity science?? We are waiting for it!! :)