Autophagy Changes With Age, Sex And Cell Type, Study Finds

TL;DR

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Researchers found that cellular autophagy did not follow one pattern of decline with age: results varied across cell types and between men and women. A five-person exercise pilot in adults aged 77 to 88 suggested activity may alter autophagy in blood cells, but larger studies are needed.

Autophagy, the process cells use to break down and recycle damaged material, does not appear to decline uniformly with age, according to a study published September 27 in Aging Cell. Researchers at Sanford Burnham Prebys Medical Discovery Institute found that patterns varied by cell type and sex in healthy volunteers, challenging a common assumption about cellular aging and highlighting limits in how the process is measured.

The team studied skin and blood samples from volunteers aged 23 to 72 who reported having no chronic diseases. Researchers also converted skin cells into induced neurons, allowing them to compare findings across three cell types. They analyzed RNA transcripts related to autophagy genes and separately measured the rate of autophagy in cells, distinguishing gene expression from the recycling activity itself.

Results differed across the groups. Autophagy declined with age in tests of male skin cells, stayed stable in female skin cells and increased in female induced neurons. The researchers also found that levels of autophagy-gene expression did not track with direct measurements of cellular recycling rate. The study therefore cautions against using gene expression alone as a stand-in for autophagy activity.

The team also examined links between autophagy and physical function among adults aged 70 and older. Higher autophagy was associated with poorer measures in that group: blood-cell activity with lower aerobic fitness, skin-cell activity with higher body mass index, and induced-neuron activity with lower grip strength and metabolism and higher resting heart rate. These are associations; the findings do not establish that autophagy caused the differences in physical function.

Why One Aging Pattern Does Not Fit All

The findings matter because autophagy is being studied as a possible target for healthy-aging interventions. If its activity differs by age, sex and tissue, a single measurement or intervention may not represent what is happening throughout the body. The results also complicate the assumption that increasing autophagy is necessarily beneficial at every age.

In the older participants, higher activity was linked to poorer physical-function measures, while the researchers said elevated autophagy may have different implications in younger adults. Those observations do not show that lowering autophagy would improve health. They instead point to the need for studies that test cause and effect and account for which cells are measured and who is being studied.

How Researchers Measured Cellular Recycling

Autophagy helps cells break down and reuse damaged or unwanted material. A decline in the process is often described as a feature of aging and has been associated with age-related conditions, including cancer, cardiovascular disease, diabetes and neurodegeneration. The study authors said evidence for a simple decline in autophagy among humans is limited.

Senior and corresponding author Caroline Kumsta, an assistant professor at Sanford Burnham Prebys, said the study was designed to examine what happens in healthy individuals rather than assume the pattern. Lead author Tatiana Moreno, a former graduate student in Kumsta’s lab, said the team wanted to challenge existing assumptions. The work appeared in Aging Cell on September 27, 2026.

“Autophagic activity changes were not universal throughout the body and did not follow the idea that autophagy simply declines with age.”

— Caroline Kumsta, senior and corresponding author

Limits of the Findings and Exercise Pilot

The study involved a limited group of healthy volunteers, and the report does not specify the total number of participants in the main analysis. Its findings do not establish whether the observed patterns apply to people with chronic illnesses or to populations beyond those studied. The links between higher autophagy and physical-function measures are observational and cannot show that one caused the other.

The exercise test was especially small: five adults aged 77 to 88 provided blood samples before and after a 12-week mild program focused on fall prevention. The results suggested that exercise may reduce blood-cell autophagic activity toward levels seen in younger people while physical performance improved. The pilot cannot establish that exercise caused the changes, or that the same pattern occurs in other cell types. The report does not provide a detailed effect size or enough information to judge how durable the changes may be.

Larger Studies Will Test Exercise Effects

The researchers said larger studies with more participants and improved testing protocols are underway with UC San Diego’s Exercise and Physical Activity Resource Center. The work follows a pilot supported by a grant from the university’s Altman Clinical and Translational Research Institute.

Those studies may help determine whether exercise consistently changes autophagy in older adults, how those changes relate to physical function, and whether results differ among tissues or by sex. Until stronger evidence is available, the current findings describe early research rather than a basis for treatment recommendations.

Key Questions

What did the study find about autophagy and age?

It found no single age-related pattern across the cells studied. Autophagy declined in male skin cells, stayed stable in female skin cells and increased in female induced neurons.

Does higher autophagy mean better health?

The study does not establish that. Among participants aged 70 and older, higher autophagy was associated with poorer measures of physical function, but association does not show cause and effect.

Did exercise change autophagy in the study?

A pilot involving five adults aged 77 to 88 suggested that a 12-week mild exercise program may reduce autophagy activity in blood cells. The small pilot is not enough to confirm an effect.

Can gene-expression tests show how much autophagy is happening?

Not reliably on their own, according to this study. The researchers found that autophagy-gene expression did not correlate with their direct measurements of cellular recycling activity.

Source: rss