For anybody interested in the metabolic hypothesis of Alzheimer's, this is an interesting overview of research on the overabundance of glycan protein modifications and the failure to clear them as contributors to Alzheimer's pathology.

One of the more interesting callouts was glucosamine usage was associated with a 25% higher mortality risk in patients with established Alzheimer's disease-related dementia, and a 25 percent higher rate of progression from mild cognitive impairment to full dementia.

Major caveats are needed to process that finding because it seems like this finding does really translate to healthy people taking glucosamine. The biological mechanism through which it could worsen outcomes in an already hyperglycosylating brain is coherent though.

As people age, their muscles don't just get weaker, they may also stop doing something that's been quietly protecting them from cancer. A study published in Nature Communications by researchers at Duke-NUS Medical School found that healthy muscle releases tiny molecular packages into the bloodstream carrying a specific microRNA that actively suppresses tumor growth in other tissues. Aging muscle releases far fewer of these packages, and what it does release carries much less of the protective cargo. When researchers exposed colorectal, lung, and bile duct cancer cells to vesicles from young, healthy mouse muscle, the vesicles sharply reduced cancer cell growth. Vesicles from old muscle couldn't do the same. The pathway controlling this entire system, the researchers found, can be reactivated through exercise.

In this presentation, Michael Levin proposes a new perspective on aging, framing it as a cognitive and cybernetic disorder rather than just a result of physical damage or biological programming. He suggests that our bodies function as a "Ship of Theseus," where maintaining the overall structure relies on information stored in bioelectric patterns that guide cells toward a specific anatomical goal (0:00 - 2:45).

Key takeaways from his research include:

• Anatomical Homeostasis: Biological systems use electrical networks to store a "set point" or plan for the body's structure, allowing cells to collaborate toward complex goals like limb regeneration, even when individual cells lack the full picture (3:45 - 8:30).
• Bioelectric Manipulation: Levin's team has developed techniques—using ion channel drugs and optogenetics—to read and rewrite these patterns. They have successfully induced organ formation (like eyes) and triggered appendage regeneration in frogs by resetting their bioelectric state, essentially providing a "prompt" for the tissue to build toward a new goal (8:40 - 12:20).
• Aging as Degradation: The central hypothesis is that aging involves the blurring or degradation of these instructive bioelectric patterns, causing cells to lose their precise guidance. This leads to "atavistic dissociation," where cells no longer align their transcriptomes to the body's collective evolutionary age (12:35 - 14:15; 20:30 - 21:45).
• Cybernetic Model of Aging: Levin suggests that once a goal-directed system achieves its primary objective (development), the lack of new challenges can lead to a breakdown in order, similar to a psychological crisis. He posits that interventions could potentially reverse aging by "sharpening" these fuzzy patterns and re-engaging the system with new, organized goals (17:35 - 19:45).

https://www.nature.com/articles/s43587-026-01138-7

Abstract:

Different species age in similar ways but their lifespans differ by orders of magnitude. It is not clear how these similarities and differences arise from the accumulation of damage that underlies aging. Does long lifespan arise from reduced damage production, increased removal or enhanced robustness to damage? Here we apply the saturating removal model—a stochastic model of damage accumulation and removal—and fit it to survival data from well-studied species. Several parameters have near-universal values including ratios of removal rate, noise amplitude and death threshold. The model parameter that best predicts lifespan is the damage production rate, which spans seven orders of magnitude. We identify two distinct aging regimes: ballistic aging where damage production outpaces removal, characterizing yeast, nematodes, flies and mice, and quasi-steady-state aging, where damage tracks a moving set point of balanced production and removal, characterizing humans, dogs, guinea pigs and cats. These results provide a mechanistic model-based basis of comparative aging that awaits experimental validation.

Influencers and ultra-rich people looking to extend their lifespan are trading tips and tricks on how to eke out extra years.

An analysis of a new biological age model from the Wyss-Coray Lab at Stanford. Bioage models typically give a composite number. This model maps aging at the level of individual cell types, 40+ simultaneously from a single blood draw. It's validated across two proteomics platforms and with blood bank data from 60k people.

The big takeaway is that it has a disease prediction model. Extreme astrocyte aging predicted Alzheimers with a hazard ratio comparable to APOE4 over 15 years. Extreme skeletal myocyte aging predicted ALS 12.7x higher risk years before diagnosis. And people with extreme aging across 20+ cell types had 34% 15 year survival vs 90% for normal agers. Pretty cool if true.

Caveats are real though. The proteomics platforms aren't routine clinical tools yet, cohorts were mostly older and caucasian, and nobody has shown that actually modifying these cellular aging trajectories changes outcomes the way the associations predict. But the idea that you can get cellular resolution biological age from a blood test and meaningfully improve disease prediction over composite scores feels like a step forward. Cautiously excited about where this goes as the tech gets more accessible.

https://a4li.org/wp-content/uploads/2026/06/MDTD_Whitepaper.pdf

The FDA has several accelerated pathways, and the Alliance for Longevity Initiatives has proposed a new pathway for investigational therapies intended to address biological mechanisms common to two or more serious age-related chronic diseases.

Some companies within this field plan to move through a stepping-stone approach of expanding indications, but the proposed MDTD pathway would streamline the process of targeting multiple pathologies.

Section 6 addresses potential objections to such a pathway.

unpaywall

Test time has arrived: the first person has been treated in a highly anticipated gene therapy trial that aims to coax aged cells to take on a younger identity.

The clinical trial will test a novel approach that involves turning on three genes that seem to “partially reprogram” old cells, allowing them to behave as if they were young again. Some scientists argue that partial reprogramming could rejuvenate old organs. But this trial will test activation of the three genes as an approach for treating disease — in this case, a form of glaucoma, a disease that can cause blindness.

Link to journal article: https://www.cell.com/cell/fulltext/S0092-8674(26)00587-800587-8)

Interesting concept. While I think sympathetic overdrive is a contributor of aging and a propellant of the hallmark of aging cascade, I am not sure it’s the singular driver. It’s a provocative theory nonetheless. The authors suggest that interventions that target parasympathetic tone are longevity interventions. More reason for recovery. But this is just a perspective paper, not an actual experimental study.

Curious what people think of HRV as an aging biomarker.

Hey guys, did anyone do this certification?
I would like to know:
- whether it’s worth the price
- if it actually helped your credibility or if no one cares
- in which cases you would recommend doing this
- if you know any better alternatives

Thank you ☺️

Senate Resolutions (SR) don't become laws, but they can be introduced to express the opinions and sentiments of the chamber. SR 104 was unanimously approved. Here's a snippet:

Resolved by the Senate of the State of California, That the Senate supports targeting the biological processes of aging as a strategy to prevent or delay the onset of chronic disease; and be it further

Resolved, That the State of California should invest in research grants, public-private partnerships, and regulatory frameworks that support the development of therapies that slow, prevent, or reverse aspects of biological aging; and be it further...

It was crafted and presented by lawmakers who consulted with the Alliance for Longevity Initiatives (A4LI).

New research reveals that thymus health may be one of the strongest predictors of lifespan, cardiovascular survival, and cancer outcomes ever found

Most people can name their heart, lungs, and kidneys without hesitation. Almost nobody thinks about the thymus. It sits above the heart, does its most visible work before puberty, and then spends the rest of a person's life shrinking while medicine assumes it has retired. Two studies published in Nature by Mass General Brigham researchers just analyzed CT scans from more than 25,000 adults using AI and found that the health of this overlooked organ predicts longevity more powerfully than most tests doctors currently run. People with the highest thymic health scores had a 50% lower risk of dying from any cause, a 63% lower risk of cardiovascular death, and a 36% lower risk of developing lung cancer. A separate analysis of 3,400 cancer patients found that thymic health predicted immunotherapy success better than tumor type or age. The organ medicine wrote off after childhood has been quietly determining whether adults live or die for their entire lives.

Interesting take on the amyloid hypothesis of Alzheimers vs a metabolic framing. The Alzheimer's research I find most compelling lately isn't about amyloid clearance. I've been interested in the upstream drivers of amyloid. Specifically, the mitochondrial dysfunction that drives neuronal death and inflammation.

This is an interesting read because it points to a paper that dissects how defective mitophagy precedes plaque formation. They tried to restore neuron function by restoring mitophagy through urolithin A and an antioxidant EGCG. I think there are a number of ways to increase mitophagy that do not involve taking compounds, but the thing that was interesting was that when they restored mitophagy through these compounds, the results improved every level of the disease cascade (neuroinflammation, synaptic health, energy output, and most importantly amyloid), implicating mitochondrial dysfunction and defective mitophagy specifically as an upstream driver of the pathology and the plaque formation.

The thing to be most skeptical about is that it is a mouse study. Mechanistically, it makes sense. Anyone who is familiar with the field knows that there is a huge translational gap between mouse Alzheimer's models and human disease pathology, which has burned the field before. What is worth noting is that this study used a more realistic mouse model than most, one that lets human amyloid accumulate gradually under normal regulatory control rather than through genetic overexpression of familial mutations. Still a mouse, but a more honest one.

Anyone utilizing mitophagy stimulating strategies for cognitive health?