The ARDD 2020 Meeting
I have spent the last four mornings watching the Copenhagen-based Aging Research and Drug Discovery (AARD) Meeting. Here are some comments on what I learned.
Day 1
I was late, but managed to get online in time to view Steve Horvath's talk on methylation-based aging clocks. A lot of it was about comparisons from applying the method to various mammal species. However, he did briefly address a topic that is of more direct interest for anti-aging research and interventions: correlation vs. causation in resetting the methylation clock. In other words, if you use an intervention that lowers your DNA-methylation age (e.g. GDF11, Katchner's Elixir, or the Conboy's plasma replacement), does this mean that you are effectively younger? Has your DNA been reprogrammed to a more youthful profile? The answer seems to be that he thinks perhaps that is the case, but it's still a guess.
The problem is that the DNA methylation test uses a chip with many thousands of "pockets" representing methylation at very many DNA sites, and it is up to the researcher to decide which of these should be used. This choice is usually done by statistically finding those having the best correlation with age. That correlation may come from random chance or it may come from seeing the actions of epigenetic programming in which genes are being silenced or activated as one ages. Up to now, it all done statistically, and nobody as worried much about which methylation sites fall into these two categories. (See my comments on David Sinclair's Day 4 talk below.)
Day 2
Some interesting talks (see Program), but none I will describe here.
Day 3
At 6:40 AM, Filipe Cabreiro (Imperial College London) considered the notion that part of the anti-aging effects of Metformin come from its interaction with microbes in the gut. He showed some data from mouse experiments that supported this hypothesis. The scenario seems to be that in young animals the microbes are diverse and beneficial, while in older animals they are winnowed down to a less diverse group that harm the host. If an aged animal has the old stuff cleared with an antibiotic and young-animal microbes added, it become healthier. (This suggests to me that an aging human like me might combine the senolytic power of Azithromycin with its antibiotic action to clear gut microbes and then drink kefir milk for several days to replace the deleted microbes with "good" ones.)
At 7:30 AM, Heidi Pak (U Wisconsin) presented evidence that the anti-aging benefits of caloric restriction come not from the reduction in caloric intake but from the decreased range of times during the day when food is eaten. This is congruent with a previous talk documenting that food input should be restricted to 10 hours out of a 24-dour day. (Moral: skip breakfast?).
At 7:50 AM, Penelope Andreux (Amazentis, Inc., Switzerland) made a convincing case for taking Urolithin A as a supplement (sold as MitoPure by her company) for revitalizing mitochondria and improving your muscles and muscle recovery time. (I looked up the product on the Internet, decided it was overpriced, and instead ordered from Amazon some Pomegranate concentrate, which is reputed to contain an unspecified amount of Urolithin A.)
At 8:20 AM, Ana Maria Cuervo (Albert Einstein College of Medicine) discussed importance of the cellular process of "chaperone mediated autophagy" (CMA) as an important lysosome-based "garbage disposal" mechanism that deteriorates with age. This suggests an anti-aging intervention involving a CMA Activator. Apparently, QX77 is such an activator, as is Humanin. (I haven't ordered any, but I'm considering it.)
At 10:20 AM, Rafael de Cabo (National Institute of Aging) spoke about using Disulfiram (AKA the prescription anti-alcohol drug Antabuse) as a way of controlling body weight in obese mice. (If you are an obese non-drinker, this might be worth considering. Eat all you want, and lose weight too!)
Finally, at 10:40 AM, Judy Campesi (Buck Institute, LBNL) gave the talk I had been waiting for on senolytic drugs. The talk was well done, and I learned a few things. She made the points that (a) the fraction of senescent cells in a given cell-type population normally never gets above 10%; (b) no senolytic drug kills all of the senescent cells; (c) senolytic compounds are both natural and synthetic, and (d) many senolytic drugs are failed anti-cancer drugs. (I think the last point reflects her association with Unity Bio, which has done an unsuccessful 2nd stage trial with a toxic anti-cancer drug aimed at knee repair, and has distinguished itself mainly by sucking up almost all of the investor capital available for commercial senolytic research). She distinguished between a senolytic drug, which clears senescent cells, and a senostatic drug, which reduces the SASP damage caused by cellular senescence. She pointed out that the latter usually require continuous application and run the risk of cumulative negative side effects. For this reason, she said that she preferred senolytics to senostatics. Perhaps the most disappointing thing about this talk about senolytic drugs was that she did not mention a single senolytic drug or make any comparisons between alternatives.
Day 4
At 6:20 AM, Laura Niedermhofer (U Minnesota) presented some mouse studies indicating that burst-doses of Fisetin do indeed clear senescent cells. She had old mouse body-maps showing the high-senescence sites and their reduction from Fisetin senolytics. However, the most interesting part of her talk was the finish, where she examined the question of whether senescent cells provide a doorway to corona virus infection and whether clearing senescent cells can provide some immunity. (A few months ago I posted that question to this GRG list. I am still not aware of anyone who has done D+Q or Fisetin senolytics and has subsequently contracted COVID-19.) Niedermhofer requested that the details of her work not be disseminated before publication, but the bottom line is that mice can be made more immune to a COVID-like corona-virus by clearing their senescent cells. (Get out your Fisetin, everyone!)
At 6:40 AM, Dudley Lamming (U Wisconsin) presented evidence that branched-chain amino-acids (BCAA: Leucine, Isoleucine, and Valine), which some people take as supplements, are bad for you. For mice, diets that restrict BCAA intake lead to extended healthspan and longevity. In the next talk, Andrey Parkhitko (U Pittsburgh) made a similar case for avoiding the non-essential amino acid Tryosine, at least for aging subjects..
At 10:00 AM, Gerard Kersenty (Columbia U) made a convincing case that the protein Osteocalcin, which comes from bone marrow, improves muscle function. (I foresee a new generation of athletes doping with Osteocalcin.)
Finally, at 10:40 AM, David Sinclair (Harvard) talked about epigenetic reprogramming. Much of it is in his book and we have heard before, but he presented new evidence that in mice, when you change DNA methylation to a younger profile, the subject mouse does demonstrate many aspects of being younger. [To me, this raises the level of importance of anti-aging interventions (GDF11, Katchner's Elixir, the Conboy's plasma replacement, etc.), which seem to reset the DNAme to a younger profile.]
Conclusion
Next year the AARD Meeting will be in New York, and it probably won't be possible to "attend" it online. The AARD web site says that recordings of the 2020 ARDD talks should be available next week. This will give some of us the opportunity to sample what we missed due to the time-zone problem. It was a very interesting meeting. However, I really wish that future presenters at such conferences would avoid acronyms, or at least define them at the bottoms of their slides, have intelligible labels on the axes of their graphs (preferably not in Russian!), and give a brief summary of what they learned at the end of the talk. I spent a lot of time Google-ing mystery terms and acronyms while I would rather have been listening.
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Was at ARDD2020 too after several times participating in person and my first on-line. You might all like to check the conference proceedings too:
Mkrtchyan GV, Abdelmohsen K, Andreux P, Bagdonaite I, Barzilai N, Brunak S, Cabreiro F, de Cabo R, Campisi J, Cuervo AM, Demaria M, Ewald CY, Fang EF, Faragher R, Ferrucci L, Freund A, Silva-García CG, Georgievskaya A, Gladyshev VN, Glass DJ, Gorbunova V, de Grey A, He WW, Hoeijmakers J, Hoffmann E, Horvath S, Houtkooper RH, Jensen MK, Jensen MB, Kane A, Kassem M, de Keizer P, Kennedy B, Karsenty G, Lamming DW, Lee KF, MacAulay N, Mamoshina P, Mellon J, Molenaars M, Moskalev A, Mund A, Niedernhofer L, Osborne B, Pak HH, Parkhitko A, Raimundo N, Rando TA, Rasmussen LJ, Reis C, Riedel CG, Franco-Romero A, Schumacher B, Sinclair DA, Suh Y, Taub PR, Toiber D, Treebak JT, Valenzano DR, Verdin E, Vijg J, Young S, Zhang L, Bakula D, Zhavoronkov A, Scheibye-Knudsen M. ARDD 2020: from aging mechanisms to interventions. Aging (Albany NY). 2020 Dec 30;12(24):24484-24503. doi: 10.18632/aging.202454. Epub 2020 Dec 30. PMID: 33378272; PMCID: PMC7803558.
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A link to the videos from the 2021 AARD.
https://www.youtube.com/channel/UClOnplI2mzpJlwdX3vlOMJA/videos