In adults aged 70 and older, cells that were recycling more of their own components were linked to worse physical function, according to a study from Sanford Burnham Prebys published in Aging Cell on Sept. 27. The association held across all three cell types the team examined, which is a surprise for a field that has long treated more cellular cleanup as better.
Caroline Kumsta, an assistant professor at the institute’s Center for Cardiovascular and Muscular Diseases and the senior author, and lead author Tatiana Moreno set out to test a common assumption: that the cell’s recycling process, called autophagy, declines with age. They found that the story depends on the cell type, on sex, and on how autophagy is measured.
What autophagy was measured in, and how
Autophagy is the cell’s cleanup process: it collects damaged proteins and other waste, packages them and breaks them down for reuse. The team collected blood and skin samples from volunteers aged 23 to 72 with no chronic medical conditions, and converted some skin cells into induced neurons, giving three cell types to compare. The release does not report how many volunteers took part in the main analysis.
They analyzed RNA transcripts to gauge autophagy-related gene activity and also measured recycling directly, to check whether gene expression matched what cells were doing. It often did not. Moreno cautioned against using static measures such as transcription levels to infer what is happening with autophagy, a warning aimed at studies that treat gene activity as a stand-in for the process itself.
The age trends diverged by cell type and sex, as News-Medical’s account lays out. Recycling activity fell with age in skin cells from men, stayed relatively stable in skin cells from women, and rose with age in induced neurons from women. Kumsta said autophagic activity changes were not universal throughout the body, and Moreno described the aim as challenging assumptions about what actually happens to autophagy during aging in healthy individuals. Moreno added that autophagy and aging are much more nuanced than previously assumed, and noted that interest is growing in targeting autophagy to develop new healthy aging interventions, which is the reason a clear picture of what happens in healthy people matters.
Weaker grip, lower fitness and a faster resting heart rate
Among participants aged 70 and older, greater autophagy was associated with poorer measures of physical function across all three cell types, according to the ScienceDaily report on the work. In blood cells, higher autophagy tracked with lower aerobic fitness. In skin cells it tracked with a higher body mass index. In induced neurons it was linked to weaker grip strength, lower metabolism and a higher resting heart rate.
Grip strength and aerobic fitness are ordinary physical measures, which makes the pairing easy to picture: the volunteers whose cells recycled the most were the ones who scored worse on them. The result runs against the common idea that more cleanup is protective, and the finding is a reminder that the right target for any intervention depends on who is being treated and which tissue is in play. Kumsta suggested that increased autophagy flux may be good in younger people yet problematic in older people, a hypothesis the study raises rather than settles.
Because the design is an association, the direction of cause is unknown. Higher autophagy could be a response to declining function rather than a contributor to it. The induced neurons are also lab-made cells reprogrammed from skin, not neurons taken from the body, so the grip and heart-rate links are drawn from a model of brain cells.
A five-person exercise pilot and a thin evidence base
The team added a small pilot. Five participants aged 77 to 88 completed a 12-week gentle exercise program focused on reducing fall risk, with blood drawn before and after. Preliminary results suggested the exercise may lower blood-cell autophagy toward levels typical of younger adults, and participants showed improved physical performance. The authors stress that the sample is far too small for firm conclusions.
“It is exciting to have this exercise intervention that may have a positive effect on autophagy and healthy aging,” Kumsta said, according to the Newswise release. Larger studies with UC San Diego’s Exercise and Physical Activity Resource Center are underway, and the work was supported by the National Institutes of Health, including the National Cancer Institute and the National Institute on Aging, along with the American Foundation for Aging Research, the Conrad Prebys Foundation and other philanthropic funders.
On the broader question, Kumsta was blunt about the state of knowledge: “the actual evidence for this in humans is very thin.” Her institute’s earlier work in roundworms, reported in a 2017 release, found an age-dependent decline in autophagy in every tissue examined, so the animal and human data point in different directions. The human paper is catalogued under its Aging Cell DOI for readers who want the full methods.
This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.
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