In people with heart failure compared with healthy controls, the gut microbiome changes and that is linked to severity of heart dysfunction and outcomes @NatureCVR nature.com/articles/s44161-0…

A Mayo Clinic team just built the cleanest causal test I've seen for NAD's role in aging. They engineered mice whose NAD synthesis depends entirely on dietary niacin, then pulled the niacin. Result: kyphosis, muscle and bone loss, cataracts, frailty, cellular senescence, shortened lifespan. Put niacin back and most of it reverses, without fully restoring NAD. That partial-restoration gap matters. It says NAD depletion triggers senescence programs that do not simply snap back when the cofactor returns. We flagged senescence as a load-bearing hallmark in the Biomarkers of Aging Consortium work (Moqri et al., Cell 2023); this is a rare in vivo model that makes the causal chain from cofactor to senescence to phenotype explicit and reversible. Nat Commun, Benitez-Rosendo, Chini et al. doi.org/10.1038/s41467-026-7…

Adrian V. Cioanca et al. from The Australian National University use a multiomics approach to reveal novel miRNA–mRNA–protein expression profiles in the aged female retina. doi.org/10.1167/iovs.67.11.3…

Does whole-grain intake reduce cardiovascular disease risk factors? And, if so, what parameters, and how much whole-grain intake? Results from 87 randomized clinical trials. Yes. Highest benefit seen at 60-100g/day = 4-6 servings See Table for each parameter and level of certainty academic.oup.com/eurheartj/a…

Somatic mutations in cells increase with age throughout our body. A new study finds they are reduced with caloric restriction, at least in mice. That hasn't been previously demonstrated @CellCellPress cell.com/cell/fulltext/S0092…

Review article by Kaleb S. Abbott from the University of Colorado Denver discusses potential harms of ocular and periorbital topical vitamin A application. doi.org/10.1167/iovs.67.11.1…

Hi all, The Lp(a) HORIZON trial has released topline data and, quite shockingly, missed its primary endpoint. In other words, lowering Lp(a) in patients with prior MI, stroke or peripheral arterial disease, who were otherwise very well treated for LDL-C, blood pressure, diabetes and other risk factors, did not reduce the primary cardiovascular endpoint. We obviously need to see the full data before making firm conclusions, and I don’t want to speculate too much without the details. But this is a big enough result that it is worth summarizing what we know, what we don’t know, and what this may mean for our patients after 20+ years of trying to test the “Lp(a) hypothesis.” What we know: 1-There are hundreds if not thousands of genetic, epidemiologic and Mendelian-randomization studies showing that elevated Lp(a) is associated with MI, stroke, peripheral arterial disease and aortic stenosis. That body of evidence is very strong. 2-However, much of those data come from community-based populations, often before the era of intensive LDL-C lowering and modern secondary prevention. 3-There has been much less information about how much residual risk Lp(a) carries in someone who has already had an event and is then treated very aggressively. 4-HORIZON may have had some of the best-treated patients of any recent cardiovascular outcomes trial. Baseline LDL-C was about 65 mg/dL, a measured LDL-C contains the cholesterol carried on Lp(a), so in reality, 15-20 points lower. 5-In patients with very high Lp(a), if you correct LDL-C for Lp(a)-cholesterol, the actual LDL-C carried by LDL particles may have been closer to 45–50 mg/dL, perhaps even lower in some patients. 6-This raises a very basic question: Can you still demonstrate a major incremental benefit from lowering another apoB-containing particle when the underlying LDL burden has already been driven this low? What we don’t know: 1-What was the actual corrected LDL-C in these patients? I think it would be extremely informative to directly measure Lp(a)-C and calculate corrected LDL-C. This may tell us a lot about the biological setting in which pelacarsen was being tested. 2- What was the OxPL status? Our prior work has suggested that much of the pro-inflammatory biology associated with Lp(a) is related to its enrichment in oxidized phospholipids. Did OxPL fall? Did patients with higher OxPL derive more benefit? Was Lp(a) concentration actually identifying the patients with the most pathogenic particles? 3- Did we measure the right component of Lp(a) for trial inclusion? We generally measure molar particle concentration. But is molar concentration itself the main driver of risk, or is it partly a surrogate for what the particle carries? Cholesterol? Triglycerides? Oxidized phospholipids? Other proteins? Could two patients with the same Lp(a) concentration have very different Lp(a)-mediated risk? I think this question deserves much more attention. 3- Were the genetic data telling us exactly what we thought they were telling us? The genetic data are extremely compelling, but genetics reflect lifelong exposure. A clinical trial treats patients late in life, often after decades of arterial injury and after an event has already occurred. Those are not necessarily the same experiment. Could there also be some unrecognized biology linked to the LPA locus that we have not completely accounted for? That possibility should at least be considered. 3- Does very low LDL-C modify the Lp(a) risk relationship? Maybe Lp(a) is particularly important when LDL-C is higher, but its contribution becomes smaller once LDL-C is driven to very low levels. Again, we need the data. 4- Does aspirin or other antiplatelet therapy reduce part of the risk associated with Lp(a)? Lp(a) has potentially important prothrombotic effects. Almost everyone in a trial like HORIZON is receiving contemporary antiplatelet therapy. Could that blunt one component of the risk associated with Lp(a)? 5- Why are these patients still having events? This may be one of the most interesting questions of all. These are patients with LDL-C around 65 mg/dL, and perhaps corrected LDL-C substantially lower, yet cardiovascular events continue to occur. What is driving that residual risk? Inflammation? Thrombosis? Plaque burden that is already too advanced? Other lipoprotein characteristics? Something we are not measuring? 6- Do we need to re-examine some basic assumptions about atherosclerosis? We have spent decades focusing heavily on the quantity of circulating lipoproteins. But perhaps lipoproteins are relatively benign until they undergo biological modification in the artery wall. Oxidation may be one of those key modifications. For some patients, the answer may be to remove more particles from the circulation. For others, perhaps the better approach is to prevent their oxidation or block the downstream biological effects of oxidized lipids. The recent difficulties with anti-inflammatory approaches, including IL-6 inhibition, make these mechanistic questions even more interesting. 7- Was there something specific about pelacarsen, the degree or timing of Lp(a) lowering, advanced disease, trial duration, background therapy or patient selection that mitigated a potential benefit? We simply don’t know yet. That is why the detailed results will be so important. What does this mean for patients today? If you have already had an MI, stroke or PAD, the immediate lesson is very clear: 1- Get all of your established risk factors treated aggressively. 2- Get LDL-C/apoB very low. 3- Control blood pressure. 4- Control diabetes. 5- Don’t smoke. 6- Use appropriate antiplatelet and other guideline-directed therapies. HORIZON shows us what modern secondary prevention should look like. If you have elevated Lp(a) but have never had an event, the genetic and epidemiologic data still suggest increased lifetime risk. Until the other 4 outcome trials read out, I would continue to treat every modifiable risk factor aggressively. We should wait for those trials before drawing broad conclusions about the entire field. I think the story of Lp(a) therapy is beginning, not ending. We also need to show tremendous respect and gratitude to the patients who participated in HORIZON and to the investigators and companies that invested enormous resources to actually test the Lp(a) hypothesis, to the ultimate benefit to peole with elevated Lp(a) to best guide how to manage risk. More to come as we go forward.

How does obesity progress toward type 2 diabetes? Lipidomic profiling reveals distinct serum lipid alterations across obesity, impaired glucose tolerance, and diabetes, identifying potential lipid biomarkers for early detection. oaepublish.com/articles/mtod… #Obesity #Diabetes #Lipid

📖 Excited to share our latest review:"Sex matters in macroautophagy." Our work highlights how biological sex shapes autophagic responses, influencing aging trajectories and susceptibility to age-related diseases. sciencedirect.com/science/ch…

September is National Service Dog Month! 🐕‍🦺 This month, we’re celebrating the incredible dogs—and the people—who make these partnerships so special. For people living with vision loss, a guide dog can be so much more than a helper. They’re trusted companions, adventure buddies and partners in navigating the world with greater confidence and independence. Explore our Paws & Purpose photo gallery featuring adorable guide dogs from Leader Dogs for the Blind! 💙 bit.ly/4oXhGw4 Image Description: Golden Retriever puppy wearing a harness that reads "Future Leader Dog," sitting in a pile of fallen leaves.

I would concur that we can't really define ultraprocessed foods very well and would argue that we are pretty far away from understanding their direct health consequences. Most of what you read about them online is noise. theatlantic.com/health/2026/…

A total eclipse of the sunflower field. ☀️🌑🌻 The Moon passed between the Sun and Earth on Aug. 12, 2026, creating a total solar eclipse visible across parts of Greenland, Iceland, northern Russia, the Atlantic Ocean, Spain, and Portugal. This composite image captures the eclipse's progression over a field of sunflowers in San Millán de los Caballeros, Spain. During totality, the Moon completely blocked out the Sun, briefly revealing the Sun's outer atmosphere, or corona.

A major inflection occurs around age 50 erictopol.substack.com/p/why…

Congratulations Chris @UCSDGlassLab on this beautiful paper! cell.com/immunity/fulltext/S…

The Blue Zones—places where people supposedly live past 100 at extraordinary rates—aren't real. A 🧵 on what went wrong: bad record keeping, pension fraud, and lots of money.

Less protein, more lifespan! A comprehensive review of the merits of protein restriction for healthy aging A flip from the proteinmaxxing craze "cell.com/cell-press-blue/ful…

Serendipitously, Nathan Zemke, Bing Ren, and @JoeEcker discovered the same phenomenon using a different approach: single cell methylation. Collectively, these data show that the replacement of yolk sac microglia by monocytes starts in middle age and is ~complete by age ~80. 5/ science.org/doi/10.1126/scie…

Gaining therapeutic access to the human brain is one of the biggest unsolved problems in biomedical science. Today @nature, we uncover a massive influx of immune cells into the human brain during aging, revealing that the brain is more accessible than previously thought. 1/ nature.com/articles/s41586-0…