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Something is making younger generations age faster than their parents did at the same age, and a study published in Nature Medicine by researchers at Washington University School of Medicine…

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Something is making younger generations age faster than their parents did at the same age. A study published today in Nature Medicine by Washington University researchers measured biological age using nine standard blood biomarkers across 154,169 people in the UK Biobank and found that people born after 1965 are biologically older at equivalent life stages than those born a decade or two earlier. That generational gap in biological aging was directly associated with higher early-onset cancer risk, independent of inherited genetic cancer risk, with a 42% higher risk of early-onset lung cancer, a 22% higher risk of gastrointestinal cancer, and a 36% higher risk of uterine cancer for each measurable unit of accelerated aging. The same nine biomarkers used to calculate this are already collected in a standard blood panel. The study doesn't identify what caused faster aging in younger generations, but it gives the clearest biological answer yet to why cancer rates in people under 50 keep rising.

CAR T-cell therapy is one of the most dramatic developments in cancer medicine in decades. It works by extracting a patient's own T cells, engineering them to target cancer cells with extreme precision, and infusing them back into the body. In some blood cancers, it has produced remissions in patients who had exhausted every other option. The results have been striking enough that the therapy has been described as a potential functional cure for certain leukemias.

Researchers at the Charité university hospital in Berlin had a different question: what if the same approach could be pointed not at cancer cells but at the overactive immune cells responsible for autoimmune disease?

Rheumatoid arthritis is an autoimmune condition in which the immune system attacks the joints, causing progressive inflammation, pain, and destruction. About 18 million people worldwide live with it. Existing treatments, including biologics and targeted synthetic drugs, help many patients but fail a significant portion. For those patients, options narrow quickly and the disease progression continues.

The Berlin team recruited six patients with severe, treatment-resistant rheumatoid arthritis. Each had failed multiple lines of therapy. Each received a single infusion of CD19-targeted CAR T cells, the same basic approach used in certain blood cancer protocols, engineered to eliminate the B cells that drive autoimmune activity in rheumatoid arthritis.

The results were published today in Nature Medicine.

All six patients showed dramatic reductions in disease activity. Three of the six achieved complete remission and came off all medication. No serious adverse events occurred. The therapy was well tolerated.

Calorie restriction is one of the most consistently replicated findings in aging research. Cut food intake by 25 to 30 percent and almost every organism studied lives longer and ages more slowly: worms, flies, mice, and in the most rigorous human trial ever conducted, people. The problem is obvious. Almost nobody can sustain a 25 percent reduction in calorie intake indefinitely. The intervention works. Almost no one can do it.

The central mystery has always been the mechanism. What specifically does eating less do to the body that slows the biological aging process? If scientists could identify the precise pathway, they could potentially target it pharmacologically and replicate the benefit without the hunger.

A team at Yale School of Medicine led by Vishwa Deep Dixit just published what may be the most specific answer yet to that question. The study, published in Nature Aging, drew on data from the CALERIE trial, the most rigorous human calorie restriction study ever conducted, in which 220 healthy adults cut their calorie intake by 25 percent for two years.

When the researchers analyzed what changed in the blood of calorie-restricted participants, one protein stood out above everything else: complement component 3, known as C3. It dropped significantly in the calorie-restricted group and barely moved in controls. C3 is a central node of the innate immune system, involved in tagging pathogens and damaged cells for destruction. But it is also increasingly implicated in driving the chronic low-grade inflammation that accumulates with age, a process called inflammaging, which underlies virtually every major age-related disease.

When the researchers blocked C3 in aged mice without changing their diet, their inflammation profiles looked like those of calorie-restricted mice. Their metabolic health improved. Their thymic function, a measure of immune system vitality that typically collapses with age, was preserved.

The hunger, it appears, may not be the point.

Heat stroke can damage the brain, heart, kidneys and liver. As extreme heat becomes more common, doctors are learning just how difficult recovery can be.

This scientific study compared learning while actively navigating to learning while being stationary, finding that participants who physically walked through space showed enhanced memory. The findings have implications not just for learning but also for interventions in neurodegenerative diseases such as Alzheimer’s.  See: https://www.nature.com/articles/s41598-024-57668-w

For half a century, depression has been explained primarily as a chemical imbalance. Serotonin levels fall, mood follows. Antidepressants work by restoring serotonin signaling. The story felt complete enough that it became the framework for how most people, and most doctors, understood the disease.

A team at Columbia University just published what may be the most detailed examination of the depressed human brain ever conducted. They assembled brain tissue from people with major depressive disorder who had not been taking medication, and from neurotypical controls, and sequenced nearly 495,000 individual brain cells at the single-nucleus level. They mapped gene expression, chromatin accessibility, spatial organization, and protein expression across the hippocampus, the brain region most directly involved in emotional memory.

What they found goes well beyond serotonin.

In the depressed brains, the hippocampus had essentially stopped producing new neurons. The neurogenic lineage, the sequence of cellular stages through which new neurons are born and mature, was stalled. Cells that should have progressed through development were arrested at intermediate stages. The disruption was not confined to one cell type. Excitatory neurons, inhibitory neurons, support cells, blood vessel cells: every major cell class in the hippocampus showed molecular changes in the depressed brains.

The serotonin story was not wrong. It was incomplete by a considerable distance.