Longevity roundtable—the science of aging, geroprotective molecules, & lifestyle interventions - More Good Stuff

Click “more” under video to see subject transcript. Handy, since almost 3 hours long.

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We discuss:
0:00:00 - Intro
0:01:07 - The recent rise in public interest in longevity, misconceptions, and the link between healthspan and lifespan
0:10:54 - Redefining healthspan, the US healthcare paradox, and separating longevity science from commercial hype
0:20:48 - The need to redirect medical research from disease-specific models to aging-focused approaches
0:30:19 - Proactive healthcare: rethinking health, disease, and the role of aging
0:35:36 - Biologic age versus chronologic age, and the limitations and potential of epigenetic clocks
0:51:42 - The utility and drawbacks of the “hallmarks of aging” as a framework for research and funding
0:59:22 - The role of epigenetic changes in aging and the challenges of proving causality
1:07:08 - The translational challenges of moving aging research from preclinical studies to human applications
1:22:23 - Distinguishing between a biomarker of aging and aging rate indicators
1:26:32 - The difficulties of translating longevity research in mice to humans, and the difficulties of testing interventions in humans
1:42:45 - Exercise, aging, and healthspan: does exercise slow aging?
1:48:26 - Are GLP-1 receptor agonists geroprotective beyond caloric restriction effects?
1:54:15- The role of senescent cells in aging, challenges with reproducibility in studies, and differing views on the value of current research approaches
2:09:46 - How funding challenges and leadership in NIH and other institutes impact the advancement of aging-related research
2:12:11 - Metformin: geroprotective potential, mechanisms, and unanswered questions
2:21:45 - Canagliflozin and rapamycin as geroprotective molecules: mechanisms, dosing strategies, and longevity potential
2:35:22 - Resveratrol and NAD precursors—a lack of evidence for anti-aging effects
2:43:17 - The potential of parabiosis and plasmapheresis to slow aging, the challenges in translating mouse studies to humans, and possible design for human studies

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Is there any new information in this?

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No but these guys are useful for letting the hot air out of the longevity irrational exuberance ballon.

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I love this. Just something pleasant to watch or listen to. We’re in a really good place. Sad to hear Richard Miller believes there’s a near zero chance funding for aging will increase in the NIH.

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Not really. Wished they spoke about more individual supplements/drugs but I still enjoyed the discussion. Makes for good step count listening.

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I just finished listening to this podcast. Mostly stuff people here would already know, but a few good points I had not heard anywhere else.

What I found particularly interesting was Richard Miller’s commentary on the GPLD1 enzyme (and Irisin). Apparently it may be a good proxy, or biomarker, for things that improve longevity. All the long-lived mice strains that Richard is familiar with have higher levels of GLPD1, exercise increases GLPD1, and its closely associated with improved cognitive performance, and the longevity drugs they’ve looked at seem to increase levels of GPLD1. So this will be something to follow going forward. Related: Irisin Ameliorates Age-associated Sarcopenia and Metabolic Dysfunction

See this part of the discussion (video set at the start point where Rich discusses this):

Richard Miller also had some interesting new information on the Linda Patridge Rapamycin / Trametinib research relating to MEK / ERK. It sounds like trametinib acts on an independent pathway that rapamycin does (the MEK - ERK pathway) and is a good promoter of chaperone-mediated autophagy, which (from the sound of it) is distinctly different from the autophagy that rapamycin promotes. So this study continues to be extremely interesting, and I would just like to see a little more data, or another study with better control mice (longer lived): A Combination of Rapamycin and Trametinib Extended Maximum Lifespan by up to 35%

See this part of the discussion (video set at the start point where Rich discusses this):

And a good update and discussion related to rapamycin and the current state of the knowledge, dosing strategies, etc., see here:

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Thanks, RapAdmin, I too though these points were interesting. I wonder if one can target GLPD1 with other drugs than the ones we already know (of course exercise etc.). Is it easily trackable with tests etc.

Gives me rapamycin vibes but for cognition:

The occurrence of AHN [adult hippocampal neurogenesis] has been demonstrated across the entire mammalian phylogenetic scale, including rodents, humans and non-human primates.

Previous work by Villeda et al.5 demonstrated that transferring blood from young to aged mice rejuvenates the systemic inflammatory milieu, increases AHN and improves cognition. The new study by Horowitz et al.1 takes one step further and shows that the beneficial effects of physical exercise on AHN and cognition can be transferred to sedentary aged mice by injecting them with the plasma of exercised animals (Fig. 1). They show that the benefits of receiving plasma injections from exercised mice occur regardless of the age (mature vs. aged) of the donor.

Just make sure your “blood boy” is exercising and you don’t have to.

https://www.nature.com/articles/s41392-020-00305-5

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I now see you kidnapping people just after they leave the gym to drain their blood :wink:

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Well… I do avoid the sun… so it makes sense.