Studies seem to show that research is becoming less ‘disruptive’ of established ideas. And this is a problem. @Nature

Calorie restriction can increase lifespan by ~40% - but a stunning study showed that it's NOT because of fat loss or insulin sensitivity. In fact, the animals who were the fattest actually lived the longest! (🧵1/8):

A new paper in @Nature from David Reich, @aliakbari23 and colleagues breaks the conventional understanding of recent human evolution. The field believed that strong selection in the recent past (~10,000 years) was rare, with few exceptions like the lactase persistence locus. In this paper, the authors challenge that belief, showing that we weren't looking at the problem right. Previous studies that looked for evidence of selection using ancient DNA addressed the problem cross-sectionally, asking if allele frequencies differed across populations more than what one would expect based on genetic drift and migration. Most arrived at the conclusion that population structure primarily explained the observed differences. Here, the authors addressed the problem longitudinally, accounting for when ancient individuals lived by explicitly modeling time as a variable in the analysis. It turns out doing it this way dramatically increases power, increasing the number of genome-wide significant selection signals by 20-fold! Looking at why accounting for the time variable led to such dramatic changes in results, the authors find that previous studies missed so much because selection often happened not on new variants leading to dramatic sweeps (the conventional model: new variant -> selection -> increase in frequency) but on already existing variants driven by transient environmental pressures. Many of these variants underwent reversals, selected up when a pressure existed, then purged when it disappeared or the trade-off cost became dominant. A great example is the TYK2 variant, where an allele boosting immunity was selected for thousands of years because it protected against TB, then got purged as TB endemicity declined and the autoimmune cost took over. The scale of what they found is striking: hundreds of loci showing strong selection in the past 10,000 years with a median selection coefficient of ~0.86%. This number is pretty big in evolutionary terms, meaning allele frequencies have been shifting by ~1% per generation in a consistent direction. Previous selection scans found a maximum of 20 loci, and this one finds hundreds. That isn't an incremental change. It fundamentally reframes our understanding of how common strong selection has been in recent human history. Some of the most striking findings come from polygenic selection, where hundreds of small-effect alleles were pushed in the same direction simultaneously. Polygenic scores based on large-scale GWAS of today predict recent negative selection for traits like body fat, waist circumference and schizophrenia, and positive selection for others like cognitive traits. One important caveat is that GWAS phenotypes are measured in industrialized societies today, and how well they capture what was actually being selected in ancient environments is debatable. For me personally, these findings have direct implications for drug discovery. When using human genetics to find drug targets, we often fixate on the benefit and risk profiles of variants visible today. But we need to be aware that a variant's benefit:harm ratio might be environmentally contingent, and could reverse when the wrong environment manifests. An evolutionary understanding of a variant's association with traits is therefore essential. The same logic applies, perhaps even more urgently, to embryo selection. Selecting embryos based on polygenic traits is humans making permanent, heritable decisions for their offspring with a narrow view of today's environment. The ancient DNA record now shows that cost-benefit landscapes flip over time. So, an embryo carrying man-made selections is carrying those changes into an unpredictable future environment. The broader takeaway is that human evolution didn't freeze in the last 10,000 years. We just lacked the tools and datasets to see its movement. The current findings are based on European populations. I am curious to see these analyses extended to other populations too, like South Asian, East Asian and African populations, which might be holding more surprises to blow our minds. Akbari et al. Nature 2026 nature.com/articles/s41586-0…

The metabolic signature of excessive endurance exercise—A prospective study in Tour de France cyclists cell.com/iscience/fulltext/S…

Tau is central to Alzheimer's pathology — here's an amazing figure (new in Cell) on the pipeline of anti-Tau therapies They aim to hit Tau from every angle: preventing its aggregation, seeding, spread; stopping it from damaging neurons; and promoting its clearance

A massive new study on peak performance included 34,000 international top performers: Nobel laureates, renowned classical music composers, Olympic champs, and the world’s best chess players. It shows early specialization is a trap, and the road to greatness is long and varied.

What does it take to achieve the highest level of human performance? Across athletics, science, chess, and music @ScienceMagazine science.org/doi/10.1126/scie…

Happy to share our new editorial for the @BJSM_BMJ on the interpretation of statistical estimates and P-values! doi.org/10.1136/bjsports-202… @Mohamma70696197 @StevenStovitz @Lester_Domes

A dark chocolate constituent—theobromine—is linked to slower aging by DNA methylation (GrimAge) and telomere length in 2 cohorts. Published today at Aging but not yet on their website; preprint link: biorxiv.org/content/10.1101/…

What are the favorable and unfavorable gut microbiome organisms associated with health markers? And effect of dietary interventions? New report from 34,000 participants nature.com/articles/s41586-0…

For more than two decades, scientists have studied whether vaccines cause autism. The answer has been consistent: there’s no evidence they do. I compiled a list of 14 studies, covering more than 10 million children, that find no link between vaccines and autism. Vaccines save lives. Sowing distrust in them puts our children’s health at risk.

Entropy and Human Aging onlinelibrary.wiley.com/doi/…

I'd love to say lots of nice things about this invaluable preventable disease tracker from @MoNscience and team at Think Global Health @CFR_org. It's an incredible resource. But I can't get over my anger & sadness that this resource is even needed. thinkglobalhealth.org/articl…

Can you rejuvenate an old brain by giving it young immune cells? 🧠 My lab @calico put it to the test. In our new study, we replaced the brain's immune cells in old mice with young ones. The result? The old brain environment forced the young cells to age RAPIDLY. A 🧵👇

1/ 🚨 Our new paper is online in @Nature ! As its first author, I’m enthusiastic to finally share it with you all!🎉 🧠 We discovered a mechanistic link between cellular energy metabolism and the control of the need to sleep 💤 👉 nature.com/articles/s41586-0… @OxfordDPAG 🧵👇

The mechanisms by which ultra-processed foods (UPF) drive obesity, an outstanding review article "the evidence is sufficiently strong to justify immediate public health efforts to reduce UPF consumption." nature.com/articles/s41574-0…

How to modulate biological aging (body-wide, epigenetic) —Obesity accelerates jamanetwork.com/journals/jam… —Exercise slows thelancet.com/action/showPdf… @TheLancet w/ @prof_horvath

Tau fibrils drive Alzheimer's, but there are no approved therapies that directly target them This is a short peptide (discovered by Eisenberg lab, in Nature this week) that wraps itself around Tau fibrils and breaks them up:

Psychedelic science largely ignored problem of unblinding, dramatically inflating effect sizes (not even *assessed* in most studies). New study: psychedelics don't outperform antidepressants in fair comparison where both studies are unblinded. osf.io/preprints/psyarxiv/vh…

This should be required reading by all graduate students and postdocs | A brief guide to statistical analysis of grouped data in preclinical research nature.com/articles/s42255-0…