Behind the Study: Using Methylation Clocks to Evaluate Anti-Aging Interventions

Dr. Josh Mitteldorf summarizes his #research perspective #published in Volume 17, Issue 5 of Aging (Aging-US), titled “Methylation clocks for evaluation of anti-aging interventions.” DOI - https://doi.org/10.18632/aging.206245 Corresponding author - Josh Mitteldorf - aging.advice@gmail.com Author interview - https://www.youtube.com/watch?v=efgNvr5ezTk Video short - https://www.youtube.com/watch?v=YjUvpqMzCGc Abstract Methylation clocks have found their way into the community of aging research as a way to test anti-aging interventions without having to wait for mortality statistics. But methylation is a primary means of epigenetic control, and presumably has evolved under strong selection. Hence, if methylation patterns change consistently at late ages it must mean one of two things. Either (1) the body is evolved to destroy itself (with inflammation, autoimmunity, etc.), and the observed methylation changes are a means to this end; or (2) the body detects accumulated damage, and is ramping up repair mechanisms in a campaign to rescue itself. My thesis herein is that both Type 1 and Type 2 changes are occurring, but that only Type 1 changes are useful in constructing methylation clocks to evaluate anti-aging interventions. This is because a therapy that sets back Type 1 changes to an earlier age state has stopped the body from destroying itself; but a therapy that sets back Type 2 changes has stopped the body from repairing itself. Thus, a major challenge before the community of epigenetic clock developers is to distinguish Type 2 from Type 1. The existence of Type 1 epigenetic changes is in conflict with conventional Darwinian thinking, and this has prompted some researchers to explore the possibility that Type 1 changes might be a form of stochastic epigenetic drift. I argue herein that what seems like directed epigenetic change really is directed epigenetic change. Of five recent articles on “stochastic methylation clocks,” only one (from the Conboy lab) is based on truly stochastic changes. Using the Conboy methodology and a methylation database, I construct a measure of true methylation drift, and show that its correlation with age is too low to be useful. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206245 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, methylation, stochastic, entropy, programmed aging, aging clock, epigenetic clock To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM