Tatiana Moreno, the lead author and a former graduate student in Caroline Kumsta’s laboratory at Sanford Burnham Prebys Medical Discovery Institute, worked with blood and skin samples from volunteers aged 23 to 72 who reported no chronic medical conditions. Kumsta, the study’s senior and corresponding author, is an assistant professor at the institute.
The researchers turned some of the skin cells into induced neurons, giving them three types of human cells in which to examine autophagy, the system cells use to collect damaged proteins and other waste, break it down and reuse its basic components. They compared RNA transcript sequencing with a technique that directly measured the rate at which cells recycle their contents.
For decades, scientists have treated a decline in autophagy as a hallmark of ageing, drawing largely on work in yeast, worms, flies and mice. Direct evidence of such a decline in humans has remained sparse, despite the idea’s frequent appearance in review articles and grant applications.
The Sanford Burnham Prebys team found that expression levels of autophagy genes did not track the direct measure of how quickly cells were recycling their contents. Moreno cautioned that researchers using static measures such as transcription levels to infer autophagy need to take care with their interpretations.
Among participants aged 70 and older, greater autophagy activity was associated with poorer physical-function measures in all three cell types. In blood cells, higher activity was linked to lower aerobic fitness. In skin cells, it was associated with a higher body mass index. In induced neurons, it was connected to weaker grip strength, lower metabolism and a higher resting heart rate.
The patterns also differed by sex and by cell type. Recycling activity fell with age in skin cells from male participants, stayed relatively stable in female skin cells, and increased with age in induced neurons derived from female participants.
The findings were reported on 27 September 2026 in Aging Cell. A small study separately suggests that gentle exercise could help older adults recover more youthful patterns of cellular recycling.
Other research points in a different direction for chaperone-mediated autophagy, or CMA. Researchers at Albert Einstein College of Medicine reported in Nature Aging that declining CMA lets senescent cells accumulate and evade immune clearance in ageing organisms. Macrophages ordinarily remove these cells, though age-related changes in CMA can impair that process.
In mice, treatment with the compound CA77.1 restored macrophage function by boosting CMA activity, reducing senescent cell accumulation and fibrosis in several organs. Problems with autophagy have been linked to diseases including cancer, cardiovascular disease, diabetes and neurodegenerative disorders.
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