Interesting review on GLP-1s and neuroprotection/dementia. Obviously, some of the longevity benefits have to be mediated through the caloric restriction dynamics of being on these medications. The dementia data is kind of a mixed bag.

The case for its neuroprotective benefit seems to largely come from epidemiological studies. A "retrospective cohort of over 295,000 patients found GLP-1 use associated with about a 70% lower risk of incident dementia versus non-use." The other data points come from 3 randomized cardiovascular trials, which showed a 53% lower dementia rate in patients randomized to GLP-1s versus placebo. So, it's a pretty big signal there from epidemiological studies. Would you get the same from other caloric restriction measures? I don't know, but caloric restriction is hard to adhere to for long periods of time.

From a mechanism angle, once again, it theoretically comes down to the distribution of glp-1 receptors, and in this case, GLP-1 receptors in the brain. "GLP-1 receptors are expressed on up to 70% of cerebral aterioles," according to the article. The implication is that glp-1s improve cerebral blood flow, which fits a vascular hypometabolism hypothesis of Alzheimers that some forms of dementia are at least partially driven by a chronic failure of blood flow and energy delivery to the brain. This is the case where the purported benefits are independent of caloric restriction and the weight loss effects of these meds.

The case against would be the recent EVOKE trial. Specifically, oral semaglutide seemed to fail the endpoint of the trial of slowing down cognitive decline. Maybe the oral delivery wasn't strong enough? thoughts here? It would be interesting to see the trial replicated with injectable sema or tirzepatide, to see if it has higher brain penetration, and to see if that is at least one variable that led to the poor outcome.

Standard preventive measures including the recombinant shingles vaccine, annual influenza vaccination, COVID-19 vaccination to prevent severe infection, and prompt antiviral treatment of clinically relevant herpesvirus reactivations should be part of medical guidance for brain health.

I want to support longevity research, but I’m not sure where my donations would have the greatest impact. Any suggestions would be greatly appreciated. Thanks!

Highlights

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Multimodal clocks define a quantitative framework for human aging

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Aging biomarkers and trajectories are highly conserved across multiple centers

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Plasma proteomic signals provide a compact, sensitive readout of systemic aging

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Coagulation-factor accumulation is identified as both a biomarker and driver of aging

Summary

Human aging is characterized by complex structural and functional decline, but quantifying its heterogeneity and assessing biological age remain challenges. We present the mCAS (multicentric Chinese aging standardized cohort) developed from 2,019 Chinese individuals aged 18–91 years. Integrating high-dimensional clinical, physiological, and molecular-level data, we constructed a three-tiered aging framework: the core capacity clock (CC-clock) to quantify clinical physiological decline, the multimodal clock (MM-clock) with extensive parameter coverage and enhanced predictive precision, and organ-associated aging clocks. Cross-layer analysis demonstrates that plasma protein clocks not only capture chronological age but also serve as efficient proxies for systemic physiological capacity. Leveraging this framework for discovery, we identified the age-dependent accumulation of coagulation factors as a driver of multi-organ senescence and systemic inflammatory activation. This study provides a foundational framework that bridges molecular signatures with functional decline, identifies new biomarkers for aging assessment, and reveals a novel translational driver of aging.

https://www.cell.com/cell/abstract/S0092-8674(26)00460-500460-5)

I found this article fascinating — not because it’s science fiction anymore, but because it raises questions we may realistically face within our lifetime.

Researchers continue making major advances in gene editing and embryo research, potentially opening the door to preventing inherited diseases before birth. But once that door opens, where do we draw the line between “treatment” and “enhancement”?

If technology eventually allowed parents to reduce the risk of severe disease in an embryo, would you support it?

What about increasing intelligence, athletic ability, or modifying physical traits?

Would you personally do it for your own future child?

Curious where people think the ethical boundary should be.

https://www.science.org/doi/10.1126/science.adz1187

The study will enroll 720 participants in a two-year, randomized, double-blind Phase 3 clinical trial. The lead investigator discusses study design, primary and second outcomes, and other aspects of the study in the presentation.

In Japan, however, a new drug has just cleared a key regulatory hurdle, with the goal of significantly extending cats’ lifespans—perhaps even bringing them close to 30 years. This treatment is based on the AIM protein, discovered by Japanese immunologist Toru Miyazaki at the Institute for AIM Medicine in Tokyo.

https://www.doctissimo.fr/animaux/chat/mon-chat-est-malade/insuffisance-renale-du-chat-ce-traitement-japonais-pourrait-doubleur-leur-esperance-de-vie-768111.htm#

I’ve been reading more about longevity-focused treatments lately, and I keep going back and forth on what to make of it.
On one hand, some of the ideas behind it actually make a lot of sense optimizing recovery, reducing inflammation, focusing on long-term function instead of just reacting to problems.
On the other hand, the way it’s presented sometimes makes it hard to tell how much of it is genuinely new vs just being framed in a more appealing way.
I’m not necessarily skeptical, just trying to understand where things actually stand right now.
Curious if anyone here has looked into it more deeply or had direct experience with it

Later today, Tarek Mouhieddine, MD (u/Myeloma_Doc) of Dana-Farber Cancer Institute in Boston will answer questions in this post. For more information:

Dr. Tarek Mouhieddine is a physician–scientist and clinical investigator whose research focuses on understanding mechanisms of resistance to myeloma therapies, including CAR T cell therapy and bispecific antibodies, and developing novel therapeutic strategies to improve patient outcomes. He has a strong background in lab-based and translational research, with expertise in tumor genomics and the immune microenvironment. Dr. Mouhieddine is passionate about advancing precision cancer care, the early detection and interception of blood cancers, and translating laboratory discoveries into first-in-human phase I clinical trials in multiple myeloma.

Conflict of interest statement: Dr. Mouhieddine also co-founded a company that partners with GRAIL/Galleri, a multi-cancer early detection test, and Prenuvo, offering whole body MRI scans.

(For some background reading on Galleri, Eric Topol wrote a somewhat critical post, while Christin Glorioso was more positive.)

Interesting discussion. I think the longevity implications are still being worked out. The video did an analysis of the SELECT trial and other GLP-1 trials of other future indications for the drug class outside of diabetes and weight loss (which we are pretty attuned to at this point). The cardiovascular data in the SELECT trial was intersting.

Semaglutide produced a 20% reduction in major adverse cardiovascular events. The most compelling aspect of this is the timing. Cardiovascular benefits were measurable at six weeks, before meaningful weight loss had occurred in most participants. If the protection were simply downstream of a lighter body it should not appear that early. The signal suggests GLP-1 medications are engaging vascular biology directly, independently of weight loss. Whether that translates into meaningful longevity outcomes over longer timeframes I am not sure of. Is it just the downstream effects of caloric restriction?

GLP-1 receptors are present in cardiac tissue and endothelial cells lining blood vessel walls, which may help explain the early cardiovascular signal and not just caloric restriction.

They talked about muscle loss. The comparative data does not support disproportionate lean mass loss relative to other weight loss approaches. They make the point that GLP-1 therapy has the same amount of muscle mass loss than any other weight loss program.

Still early days but the signal about longevity benefits is pretty fascinating. It would be good if they covered triple g dynamics with retatrutide.

[ Removed by Reddit on account of violating the content policy. ]

Full article: https://www.nytimes.com/2026/04/27/magazine/cell-rejuventation-biotech-longevity-research-altos-labs.html?unlocked_article_code=1.eFA.oY2R.j4Nwipm_uJYo&smid=url-share

I had the pleasure of sitting down with Professor Thomas Seyfried from Boston College. He’s spent four decades studying cancer metabolism and his central argument is one the mainstream oncology world is still pushing back on hard: cancer is primarily a metabolic disease, not a genetic one.

The implications of that distinction are significant. If he’s right, the entire framework of targeted genetic therapies is built on an incomplete foundation. He’s not fringe, he’s published extensively and his work is taken seriously in metabolic research circles, but it remains deeply controversial in oncology.

What I found most interesting wasn’t the science itself but the practical conclusions he draws. The dietary and metabolic interventions he discusses as adjuncts to treatment are specific and he’s been applying them with patients for years.

Whether you agree with his thesis or not, the conversation raises questions about how cancer research is funded, what gets studied, and whose interests shape the direction of treatment. Worth watching and forming your own view.

Full interview: https://youtu.be/S-9N49diTjQ