6 ms·
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
by robwwilliams 5y ago
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
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.
- guzik 5y agoI think the correct link is www.nia.nih.gov/research/dab/interventions-testing-program-itp ?
- robwwilliams 5y agoThanks for correction.
- nradov 5y agoThis Peter Attia podcast has an excellent review of research into rapamycin as a potential longevity treatment. https://peterattiamd.com/mattkaeberlein2/ https://peterattiamd.com/mattkaeberlein2/
- JamesBarney 5y agoFor 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). Canagliflozin
- novok 5y agoHow much of the male only treatments was basically make the males less male and reducing their testosterone levels?
- rpmisms 5y agoLikely most of it. Testosterone is high-octane gas for the body. Burns hotter.
- belorn 5y agoThe answer might surprise you a bit. 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.
- banq 5y agoCaakg: https://www.aging-us.com/article/203736/text https://www.aging-us.com/article/203736/text