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

TL;DR

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A study published in Aging Cell found that autophagy did not change uniformly with age: results differed by cell type and sex, and gene-expression levels did not reliably indicate measured recycling activity. A five-person exercise pilot in adults aged 77 to 88 suggested that a 12-week program may lower blood-cell autophagy activity, but larger studies are needed.

Researchers at Sanford Burnham Prebys Medical Discovery Institute found that autophagy varies by age, sex and cell type, rather than declining uniformly as people get older. The study, published September 27 in Aging Cell, also reported that gene activity did not reliably track directly measured cellular recycling, a finding that may affect how researchers assess autophagy in studies of aging.

The team examined skin and blood samples from volunteers aged 23 to 72 who reported having no chronic diseases. Researchers also converted skin cells into induced neurons to compare several cell types. They analyzed RNA transcripts related to autophagy genes and separately measured autophagy activity, allowing them to compare gene-expression signals with the cellular process itself.

The results differed across groups and cells. Autophagic activity declined with age in male skin cells, remained stable in female skin cells and increased in induced neurons from women. The researchers also found no correlation between the expression levels of autophagy genes and their direct measure of recycling activity.

In adults aged 70 and older, higher measured autophagy was associated with poorer physical-function measures across the cell types studied. The reported associations included lower aerobic fitness alongside higher autophagy in blood cells, higher BMI with higher activity in skin cells, and lower grip strength and metabolism and a higher resting heart rate in relation to activity in induced neurons. These are associations; the study does not establish that autophagy changes caused the differences in physical function.

Why Cell-Specific Measurements Matter

The findings challenge a broad assumption in aging research: that autophagy simply decreases across the body with age. If activity varies by cell type and sex, results from one tissue or group may not describe what is happening elsewhere. That matters to researchers studying autophagy as a possible target for interventions intended to support healthy aging.

The mismatch between gene expression and measured activity also has practical implications. A static reading of autophagy-related transcripts may not show how quickly cellular recycling is occurring. The authors say researchers should be cautious about drawing conclusions from those measures alone. The study does not establish a treatment or show that increasing or decreasing autophagy improves health; its results point to the need for more specific measurement and follow-up research.

Testing a Common Aging Assumption

Autophagy is a cellular recycling process that breaks down damaged or unwanted material into components cells can reuse. Its decline is often described as one feature of aging and has been linked in research to age-related diseases. Senior author Caroline Kumsta said the human evidence behind a general age-related decline is limited, motivating the team to examine healthy volunteers directly.

Lead author Tatiana Moreno said the project was intended to test assumptions and clarify what happens to autophagy during aging in healthy people. The team combined RNA analysis with direct activity measurements rather than relying on gene-expression data alone. The report describes differences across the tested cells and participants, not a universal pattern that can be applied to every person or tissue.

“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

Limits of the Human Evidence

The source report does not provide the total number of participants in the main sample or detailed estimates of the strength and uncertainty of each association. The volunteers reported that they had no chronic diseases, so the results may not represent people with those conditions or the wider population. The study also does not show that the observed links between autophagy and physical function are causal.

The exercise finding is preliminary: it involved five adults aged 77 to 88 who completed a 12-week, mild program focused on fall prevention. The report says blood-cell autophagy activity appeared to move toward more youthful levels while physical performance improved, but it does not establish how much of either change was caused by exercise. The best level of autophagy for different ages, cell types or health outcomes also remains unknown.

Larger Exercise Studies Underway

The researchers say 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 research on exercise, autophagy and physical function in aging.

Those studies may help test whether the pilot’s blood-cell changes can be reproduced and clarify how they relate to physical performance. Until more results are available, the exercise findings should be treated as an early signal rather than evidence that a particular program changes autophagy or prevents age-related disease.

Key Questions

What did the study find about autophagy and aging?

It found that autophagy did not change uniformly with age. Patterns differed by cell type and sex, and gene-expression levels did not reliably match directly measured activity.

Did autophagy decline in all the cells studied?

No. It declined with age in male skin cells, stayed stable in female skin cells and increased in induced neurons from women, according to the report.

Does the study show that higher autophagy causes poorer physical function?

No. The researchers reported associations in adults aged 70 and older, but the study does not show that autophagy changes caused differences in physical function.

Did exercise change autophagy in older adults?

A pilot involving five adults aged 77 to 88 suggested that blood-cell autophagy activity may have decreased after a 12-week mild exercise program. The small pilot cannot establish that exercise caused the change; larger studies are underway.

Source: rss