Alan A. Cohen, PHD I Rethinking Health and Aging

What if aging is not a single program? What if health is not just “the absence of disease but rather the capacity to maintain dynamic equilibrium. A thread on why we need a science of health, not just a science of breakdown. #ScienceOfHealth #Aging

@davidasinclair Interesting paper. Calling heat therapy “exercise-like” is interesting, makes me think: It’s not the intervention itself that matters most, but the adaptive response it triggers. We can have many different inputs, similar system-level effects.

Best review yet: We have identified plausible ways heat therapy works, such as shear stress and heat-sensitive genes “We find heat therapy to be analogous to exercise in many respects” 💪 onlinelibrary.wiley.com/doi/10.1002/cp…

What appears to be amazing symptom alleviation could in fact be killing us. I had a lot of fun writing this substack post with @MitoPsychoBio on the risks of trying to meddle with the body's internal homeostatic mechanisms - in this case, the ability to detect energy shortages and make rationing decisions. substack.com/home/post/p-19…

Here I’ll share work on rethinking health and aging, evolution, complex system and building a real science of health. If you are interested in health, longevity, medicine, or the limits of reductionism, follow along. We may need to rethink the whole frame. #HealthyLongevity #DynamicEquilibrium

This points to a core problem in modern medicine and longevity culture: it treats the body like a machine to optimize, instead of a living system to understand. More inputs. More tweaking. More control. Neglecting the complex system.

What if aging is not a single program? What if health is not just “the absence of disease but rather the capacity to maintain dynamic equilibrium. A thread on why we need a science of health, not just a science of breakdown. #ScienceOfHealth #Aging

@mkaeberlein Really interesting result. Maybe that’s because health is not a mountain to climb by optimizing one thing after another, but a plateau to remain on. The biggest benefits may come less from reaching the exact center than from avoiding the cliff.

Longevity March Madness 2026 — We Have a Champion! 🧬 🏆 After weeks of matchups, thousands of votes, and a bracket that included everything from lifestyle interventions to cutting-edge geroscience... The winner is: Proactive Healthcare. In the championship matchup, the 10-seed Cinderella defeated Optimization of Metabolic Health in a decisive 67.5–32.5 victory. What makes this result so interesting isn’t just the outcome—it’s the path. Proactive Healthcare advanced through a field of 64 interventions that included: - Lifestyle fundamentals like Not Smoking and Strength Training - Evidence-based medical therapies like Vaccination and SGLT2 inhibitors - Leading geroscience interventions like Rapamycin and Caloric Restriction Along the way, it knocked off Vaccination, Maintain Oral Health, and even the #1 overall seed, Not Smoking, before closing it out in the final. The winning “intervention” wasn’t a molecule, a supplement, or a single behavior. It was a strategy. - Early detection. - Risk factor management. - Prevention before disease develops. In a field that often focuses on optimizing the margins—new compounds, novel pathways, and emerging technologies—this result is a useful reminder: The biggest impact on healthspan and lifespan still comes from systematically identifying and managing risk early and consistently. That doesn’t make the other interventions unimportant—far from it. But it does highlight something we sometimes overlook: Execution of the fundamentals matters more than any single breakthrough.

@mkaeberlein @UAZPharmacy Looking forward to the rapamycin discussion in Tucson key to separating what we know from hype. In rethinking health and aging, dosing/timing often interacts with individual biology in ways that deserve more attention.

If you’re in Tucson next week, I’ll be giving a talk at the University of Arizona College of Pharmacy (@UAZPharmacy) on the science behind rapamycin and aging. We’ll cover what we know, what we don’t, and where the field is headed. April 14, 4–5:30pm Andrew Weil Center for Integrative Medicine (@AzCIM) Would love to see you there. Register: RSVP here pharmacy.arizona.edu/events/can-dru…

@mkaeberlein Your bracket highlights how systems-level prevention can rival single-factor wins. In my work rethinking aging trajectories, population variability suggests early risk management might amplify metabolic gains even more. Curious how you'd weight individual heterogeneity here?

The Longevity March Madness Final Four is Set: Here’s a wrap-up of how the four division finals played out. Lifestyle: A heavyweight classic It doesn’t get bigger than this. Top-seeded Not Smoking held off a furious push from Strength Training, surviving 53–47 in a battle that felt like a championship game all on its own. Strength Training brought everything—power, consistency, momentum—but in the end, nothing could overcome the sheer magnitude of risk reduction that Not Smoking delivers. It wasn’t a blowout. It was a grind. And the #1 seed advances. Medicine: Cinderella keeps dancing At some point, it stops being a surprise. 10-seed Proactive Healthcarecontinued its improbable run, dismantling Maintain Oral Health 82–18 in the most lopsided result of the round. After taking down Vitamin D and Vaccination earlier, this was a statement: prevention, early detection, and system-level thinking aren’t just holding on—they’re dominating. The Cinderella story is now one game away from a title. Geroscience: The king holds court There was no upset here—just authority. Top-seeded Caloric Restriction took down Rapamycin 59–41 in a matchup that felt like the ultimate clash of longevity titans. Rapamycin came in with the strongest pharmacologic resume in aging biology, but caloric restriction reminded everyone why it’s still the benchmark. Decades of data, across species, and it still gets the job done. Biohacking: No contest This one was over early. Optimization of Metabolic Health overwhelmed Regular Sexual Activity 82–18, delivering one of the most dominant performances of the tournament. Glucose control, insulin sensitivity, and metabolic stability proved to be too much—no matter how compelling the underdog story. The #1 seed moves on, and looks stronger than ever. The bracket is set. The contenders are clear. And now we’re down to the Final Four. Not Smoking versus Proactive Healthcare Caloric Restriction versus Optimization of Metabolic Health Which interventions will punch their tickets to the championship round and which will be sent packing. You decide: optispan.life/longevity-brac…

Each cytokine plays many roles, and the overall patterns lead to a physiological response. We can't interpret them one at a time, out of context.

This challenges the assumption that the basic biology of aging is universal. Physiology is malleable and learns from our environment. Inflammation is a stress response system, and Tsimane don't have the same stressors we do.

Inflammation isn't always bad. In our amazing new study in @NatureAging, we show that inflammaging does not exist in the typical way in two indigenous populations. It doesn't increase with age and doesn't predict chronic disease at all. #Inflammation rdcu.be/et9n6

Too much competition in science leads to over-optimizing the metrics of success (publications, funding, etc.) at the expense of actual good science. It's Goodhart's law. Here's a post I wrote on it before I heard of Goodhart's law: maketheworldworkbetter.wordpress.com/2013/04/03/wha…

Can we feel our mitochondria? We feel pain (nociception), internal sensations (interoception), and even our immune system (immunoception) How does the brain monitor our energy status? In this preprint, we propose that the brain feels the balance of energy demand (burn rate) and energy transformation capacity (mitochondrial OxPhos capacity) via mitoception Cellular studies, animal models, clinical, and human studies suggest that the cytokine GDF15 is the main signal of mitoception Preprint by Cynthia Liu and colleagues @torwager @LFeldmanBarrett @Danbelsky @Dr_Epel @cohenaginglab osf.io/preprints/osf/… Comments welcome!

Impressive innovation, but we should ask if it helps us break the cycle or just feeds it in disguise. The harder work is still behavioral change.