Yes, and the tight timelines of VC and high burn rate of startup funds motivates hype and self-delusion. Longevity research requires a 20–30 year time line even if you are using mice.
But is there good news? Yes: the NIA Interventions Testing Program is an awesome, systematic, flexible, and rigorous effort to evaluate the impact of dietary supplements on lifespan.
And the 10 year studies we have just completed on the genetics of lifespan and longevity in a highly diverse family of mice (the BXD family) provide very strong evidence of gene variants that modulate longevity well after reproductive senescence and under different environments. It is NOT a matter of selection for or against lifespan: it is just a result of high levels of genetic variation affecting all biochemical processes and disease risks. Genetic variants and gene-by-environmental interactions definitely are “in play”. These types of variants are actually inevitable.
Want some references for the smoke-free and half-full part of the glass?
1. Hook et al PMC6066442: Genetic cartography of longevity in humans and mice: Current landscape and horizons.
2. Roy et al 2021 in Nature Metabolism: Gene-by-environment modulation of lifespan and weight gain in the murine BXD family; doi.org/10.1101/776559
3. Williams et al in Cell Systems 2021: Multiomic profiling of the liver across diets and ages in a diverse mouse population; doi.org/10.1101/2020.08.20.222968v2
All of the data from the last two paper is available as FAIR data at www.genenetwork.org.
You are welcome to map the longevity loci yourself. Some of these loci operate only late in life—some even after two years of age—roughly equivalent to 60 years and older in humans.
After your trauma at the meeting, read the papers above to know that solid verifiable progress is being made. And smell the ITP roses at
Rapamycin and acarbose definitely extend lifespan in highly diverse mice (a robust result) and so do several other dietary additives—at least five others at this point. Resveratrol, as you say, is a failure, and this is confirmed by well powered studies by the ITP.
For those who are looking for a summary of the ITP research.
As of Cohort 10, C2014, 7 compounds have shown significant extension of median lifespan:
Aspirin – Increased lifespan in males but not females (Strong et al., 2008).
Rapamycin – Increased mean and maximal lifespan in both males and females when initiated at 20 months of age (Harrison et al., 2009) and when initiated at 9 months of age (Miller et al., 2011). Females responded more robustly than males at equivalent doses; when ~ equal blood levels were achieved, response was also about equivalent in females and males (Miller et al., 2013).
17αEstradiol – Increased lifespan in males but not females, at 4.8 ppm dose (Harrison et al., 2013) and 14.4 ppm dose (Strong et al., 2016).
Acarbose – Increased lifespan in both males and females, but the effects were greater in males, when initiated at 4 months of age (Harrison et al., 2013), but only males responded when initiated at 16 months of age (Strong et al., 2016).
NDGA (nordihydroguaiaretic acid) – Increased mean lifespan in males but not females (Strong et al., 2008), even at doses that gave equivalent blood levels in males and females (Harrison et al., 2013).
Protandim® – Increased lifespan in males but not females (Strong et al., 2016).
Glycine – Started at 9 months. Increased lifespan in males and females (Miller et al., 2019).
It's pretty easy to extend lifespan in lab mice that live in safe, sterile cages with optimal diets. I suspect those medications all have side effects that would reduce or eliminate the net benefits in wild animals that have to contend with pathogens, injuries, predators, food scarcity, etc.
No, it is not easy. In fact, a large majority of tests have failed in the ITP.
But you are right about the major role of “extraneous” environmental factors, and this is why we started our studies with a systematic perturbation of diet—low fat versus very high fat (citations are above). The correlation of longevity on these profoundly different diets is about r = 0.6 based on an analysis of 76 balanced cohorts of strains on the two diets—about 10 females per strain per diet. With the deep replication (10 identical twins per treatment) these are rock solid data. A correlation of 0.6 gives “explained variance” of only 36% (r^2), so that highlights the major effect of diet on longevity. And the gene variants that modulate longevity on the two diets are, as expected, very different.
Bottom line: the genetics of longevity is the genetics of gene-by-environment interaction—your major point.
I see that Rapamyacin is a mTor inhibitor. From my years of lurking r/fitness my understanding is that is the “growth pathway” that you want to activate for muscle building (with whey for example). But it doesn’t look like people with more muscular mass die early, even the opposite. Am I missing something?
People who are healthier have more muscle mass but adding muscle mass doesn't make you healthier. Muscle mass is a signal of health not a cause. You can look at bodybuilding lifespan for proof. Lots of bodybuilders die young despite adding on enormous amounts of muscle.
You can see the same with testosterone. Men with higher testosterone live longer but giving people testosterone doesn't increase lifespan.
I would guess they do die early compared to people of the same activity levels, they just tend to get so much more exercise than average that the effect is overwhelmed.
Aspirin reduce inflammatory response, which testosterone also do. The more likely reason why Aspirin helps to improve lifespans in men is that it steps in when testosterone has fallen through aging, stepping in to do the role of testosterone. High inflammatory response can be quite deadly, especially in connection with cardiovascular problems (a common cause of death for men).
17αEstradiol is a weaker form of estrogen. Men that has either too high or too low amount of estrogen has an significant increase in heart failure. When testosterone goes down during old age, estrogen tend to also go down as estrogen is produced in men through converting testosterone. Again it seems that the drug can help by stepping in after a fall in testosterone.
NDGA (nordihydroguaiaretic acid) is an xenohormone that imitates estrogen. See above about estrogen.
Protandim is a mix of five herbs, including green tea. Can't tell anything about that, and FDA has issued a warning against the manufacturer for false claims.
I don't think the 17a estradiol effect is due to classic estrogenic activity. But probably due to ER-X activation which helps correct metabolic abnormalities in men.
But is there good news? Yes: the NIA Interventions Testing Program is an awesome, systematic, flexible, and rigorous effort to evaluate the impact of dietary supplements on lifespan.
And the 10 year studies we have just completed on the genetics of lifespan and longevity in a highly diverse family of mice (the BXD family) provide very strong evidence of gene variants that modulate longevity well after reproductive senescence and under different environments. It is NOT a matter of selection for or against lifespan: it is just a result of high levels of genetic variation affecting all biochemical processes and disease risks. Genetic variants and gene-by-environmental interactions definitely are “in play”. These types of variants are actually inevitable.
Want some references for the smoke-free and half-full part of the glass?
1. Hook et al PMC6066442: Genetic cartography of longevity in humans and mice: Current landscape and horizons.
2. Roy et al 2021 in Nature Metabolism: Gene-by-environment modulation of lifespan and weight gain in the murine BXD family; doi.org/10.1101/776559
3. Williams et al in Cell Systems 2021: Multiomic profiling of the liver across diets and ages in a diverse mouse population; doi.org/10.1101/2020.08.20.222968v2
All of the data from the last two paper is available as FAIR data at www.genenetwork.org. You are welcome to map the longevity loci yourself. Some of these loci operate only late in life—some even after two years of age—roughly equivalent to 60 years and older in humans.
After your trauma at the meeting, read the papers above to know that solid verifiable progress is being made. And smell the ITP roses at
www.nia.nih.gov/dab/interventions-testing-program-itp
Rapamycin and acarbose definitely extend lifespan in highly diverse mice (a robust result) and so do several other dietary additives—at least five others at this point. Resveratrol, as you say, is a failure, and this is confirmed by well powered studies by the ITP.