Centenarians Show a Distinct Metabolic Profile Tied to Bile Acids and NAD+
People who live past 100 have a unique metabolic fingerprint. In a study of 213 participants from the New England Centenarian Study, extremely long-lived individuals had higher levels of certain bile acids and lower levels of bilirubin compared to younger controls. Higher bile acid and steroid levels were linked to lower mortality risk. The researchers also built a "metabolomic clock" that estimates biological age, and deviations from it predicted death risk.
Key Insight
This study suggests bile acid metabolism and NAD+ pathways may be key targets in longevity research.
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Fat Tissue Controls Lifespan Through Insulin Signaling in Fruit Flies
In fruit flies, dialing down a gene called Dicer-1 in fat tissue extended lifespan. It worked even when flies were already on calorie restriction. The mechanism involves a chain reaction: lower Dicer-1 reduces a small RNA molecule in fat, which boosts a hormone that then tells the brain to release less insulin. Less insulin signaling is a well-known longevity pathway across species.
Eight Hyped Compounds Failed to Extend Lifespan in a Major Mouse Study
The NIA's Interventions Testing Program tested eight compounds across three lab sites in genetically diverse mice. None extended lifespan. That includes astaxanthin, alpha-ketoglutarate, pioglitazone, atorvastatin-telmisartan, and others with prior promising results. Some compounds previously shown to work at different doses or start ages didn't replicate under new conditions. Two drugs actually shortened lifespan in female mice.
New Aging Clocks Built From Histone Marks Work Across Species
Researchers built 36 new biological aging clocks using histone modifications (chemical tags on the proteins that package DNA) instead of the usual DNA methylation approach. These clocks worked well across six tissue types and could detect accelerated aging in leukemia samples and age reversal after treatments. One surprising finding: many aging-related changes peak at midlife rather than climbing steadily. The approach even worked in fruit flies, which lack DNA methylation entirely.
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