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

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A study published in Aging Cell found that autophagy did not follow a uniform age-related decline in the human cells tested. Patterns differed by cell type and sex, and a five-person exercise pilot suggested activity may alter autophagy in older adults; larger studies are needed.

Researchers at Sanford Burnham Prebys Medical Discovery Institute found that autophagy changes differently with age across cell types, and that patterns also vary by sex, challenging the assumption that cellular recycling simply declines as people get older. The study, published September 27 in Aging Cell, examined samples from healthy volunteers and included a small exercise pilot in older adults; the findings are not evidence that changing autophagy will prevent disease or extend life.

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 examine three cell types. They analyzed RNA transcripts to assess the expression of genes involved in autophagy and directly measured autophagic activity in cells.

Results differed across the groups tested. Autophagy declined with age in male skin cells, remained stable in female skin cells and increased in induced neurons from women. The researchers also found that autophagy-gene expression did not correlate with their direct measurement of cellular recycling activity, a distinction that matters when interpreting studies based only on gene-expression data.

In participants aged 70 and older, higher autophagy was associated with poorer physical-function measures across the cell types studied. These included lower aerobic fitness linked with blood-cell autophagy, higher body mass index linked with skin-cell autophagy, and lower grip strength and metabolism, alongside higher resting heart rate, linked with induced-neuron autophagy. These are associations, not proof that autophagy caused the differences.

A separate pilot involved five adults aged 77 to 88 who completed a 12-week mild exercise program focused on fall prevention. Blood samples taken before and after the program suggested that exercise may reduce blood-cell autophagic activity toward levels seen in younger people, alongside improved physical performance. The small sample means the result is preliminary.

Why Cell-Specific Patterns Matter

The findings complicate a common account of aging: that autophagy, the process cells use to break down and recycle damaged components, steadily declines throughout the body. Instead, the study reports different patterns by cell type and sex. That distinction could matter to researchers seeking to understand how cellular maintenance relates to aging and disease, and to efforts to develop interventions that target autophagy.

The results also caution against treating a change in autophagy as automatically beneficial. In the older participants, higher measured activity was associated with some poorer physical-function indicators, while the exercise pilot suggested a possible reduction in blood-cell activity alongside improved performance. The study does not establish why these patterns occur or whether they apply beyond the cells and participants examined. For now, it supports more precise, cell-specific research, not a recommendation to raise or lower autophagy.

How Researchers Measured Recycling

Autophagy is a cellular recycling process that packages damaged or unwanted material for breakdown into reusable components. Its decline is often described as a feature of aging, and impaired autophagy has been associated with age-related conditions. The study’s authors said the human evidence behind a simple, across-the-board decline is limited, prompting them to test the assumption in healthy volunteers.

The research combined two kinds of measurement: RNA sequencing, which indicates gene activity, and a direct assessment of autophagic activity, or flux. The gap between gene-expression signals and measured activity is relevant because researchers cannot necessarily infer the rate of cellular recycling from autophagy-gene transcripts alone. The study was conducted by the Kumsta lab at Sanford Burnham Prebys.

“We commonly see people cite this idea that autophagy declines with age, but the actual evidence for this in humans is very thin.”

— Caroline Kumsta, senior and corresponding author and assistant professor at Sanford Burnham Prebys

Limits of the Human Evidence

The study examined a limited set of cell types from volunteers who reported no chronic disease, and its findings do not establish how autophagy behaves in every tissue or in people with age-related illness. The reported links between autophagy and physical function are associations; the study does not show that autophagy changes caused differences in fitness, body mass index, strength, metabolism or heart rate.

The exercise finding is especially preliminary: it came from five older adults and blood-cell measurements after a 12-week program. It remains unclear whether the result would hold in a larger group, whether it applies to other cell types, or what level of autophagy would be beneficial for people of different ages and sexes.

Larger Exercise Studies Planned

The researchers said larger studies with more participants and improved testing protocols are underway with the Exercise and Physical Activity Resource Center at UC San Diego. The Kumsta lab received a pilot grant from UC San Diego’s Altman Clinical and Translational Research Institute to expand work on exercise, autophagy and physical function in aging.

Those studies may help determine whether the pilot’s blood-cell findings can be reproduced and how changes in autophagy relate to physical performance. Until further results are available, the authors’ findings remain an early step toward understanding the relationship, not evidence for a specific exercise prescription or autophagy-targeting treatment.

Key Questions

What did the study find about autophagy and aging?

It found that autophagy did not uniformly decline with age in the cells examined. Patterns varied by cell type and sex.

Which cells showed changes with age?

Autophagy declined in male skin cells, stayed stable in female skin cells and increased in induced neurons from women. The study also examined blood cells.

Does higher autophagy cause poorer physical function?

The study found associations between higher autophagy and some poorer physical-function measures in adults aged 70 and older. It did not establish cause and effect.

Did the exercise pilot prove that exercise changes autophagy?

No. The pilot included five adults aged 77 to 88. Its results suggest exercise may reduce blood-cell autophagic activity, but larger studies are needed to test the finding.

Can gene activity show how fast autophagy is happening?

Not reliably on its own, according to the researchers. In this study, autophagy-gene expression did not correlate with the direct measurement of cellular recycling activity.

Source: rss