Scientists discover a surprising paradox in how our cells age
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Cells rely on a natural cleanup system to prevent damaged materials from accumulating inside them. Known as autophagy, this process collects defective proteins and other cellular waste, packages them into specialized compartments, and breaks them down into basic molecular components that can be reused.
This recycling system helps protect cells from damage. Scientists have long considered declining autophagy a hallmark of aging, and problems with the process have been linked to numerous diseases, including cancer, cardiovascular disease, diabetes, and neurodegenerative disorders.
However, new research suggests that cellular recycling does not necessarily slow down as people get older. Instead, its activity can increase, decrease, or remain unchanged depending on the type of cell and a person’s sex. The findings also suggest that exercise may influence how this process functions in older adults.
Researchers at Sanford Burnham Prebys Medical Discovery Institute reported these findings on September 27, 2026, in the journal Aging Cell, challenging a widely accepted view of how cellular recycling changes throughout life.
“We commonly see people cite this idea that autophagy declines with age, but the actual evidence for this in humans is very thin,” said senior and corresponding author Caroline Kumsta, PhD, assistant professor in the Center for Cardiovascular and Muscular Diseases at Sanford Burnham Prebys.
“Interest is growing in targeting autophagy to develop new healthy aging interventions,” said Tatiana Moreno, PhD ’26, lead author of the study and a former graduate student in the Kumsta lab.
“We wanted to challenge assumptions and investigate what actually happens to autophagy during aging in healthy individuals.”
How Scientists Studied Cellular Recycling and Aging
To better understand the relationship between aging and autophagy, the researchers collected blood and skin samples from volunteers between the ages of 23 and 72. All participants reported having no chronic medical conditions.
The team also converted some of the collected skin cells into induced neurons, allowing the researchers to examine cellular recycling in three different cell types.
For each cell type, the scientists analyzed RNA transcripts, which are produced when cells read genetic instructions from DNA to make proteins, enzymes, and other essential components. This analysis allowed them to examine how age and cell type affected the activity of genes involved in autophagy.
Importantly, the researchers did not rely on gene activity alone. They also directly measured how quickly cells carried out autophagy, allowing them to determine whether patterns in gene expression accurately reflected the amount of recycling taking place.
The results revealed a much more complicated picture than the traditional understanding of cellular aging.
“We found that autophagic activity changes were not universal throughout the body and did not follow the idea that autophagy simply declines with age,” said Kumsta. “Rather, cellular recycling rates are altered differently with age in each of the cell types, and differently by sex in each of the cell types.”
Aging Affects Different Cells in Surprising Ways
The researchers observed striking differences in how autophagy changed with age. In skin cells from male participants, recycling activity decreased as age increased. In female skin cells, it remained relatively stable. Meanwhile, induced neurons derived from female participants showed an increase in autophagy with age.
These findings demonstrate that cellular recycling does not follow a single pattern throughout the body. Instead, aging appears to affect the process differently depending on the cells being examined and the sex of the individual.
The researchers also discovered that the expression of genes responsible for autophagy did not reliably indicate how much recycling was actually occurring. Cells with higher or lower levels of autophagy gene expression did not necessarily show corresponding differences in their measured recycling rates.
“This shows that people using static measures such as transcription levels to infer what’s happening with autophagy need to be really careful about their interpretations,” said Moreno.
Why More Cellular Cleanup May Not Be Better
The team next investigated whether differences in autophagy were associated with physical health and performance as people age.
Their findings pointed to another unexpected possibility: higher levels of cellular recycling may have different implications for younger and older adults.
Among participants aged 70 and older, greater autophagy activity was associated with poorer measures of physical function across all three cell types studied.
In blood cells, higher autophagy was linked to lower aerobic fitness. In skin cells, it was associated with a higher body mass index (BMI). In induced neurons, increased recycling activity was connected to weaker grip strength, lower metabolism, and a higher resting heart rate.
These associations suggest that increased autophagy is not necessarily a sign of healthier aging. Although cellular recycling plays an essential protective role, its relationship with physical health may change later in life.
“I think this is an important distinction that merits continued study, as it appears that increased autophagy flux may be good in younger people yet problematic in older people,” said Kumsta.
“Autophagy and aging are so much more nuanced than previously assumed,” said Moreno. “To better translate autophagy research discoveries into potential therapies, we really need to understand what is happening on a cell-specific level and how it is affected by sex and age.”
Gentle Exercise May Help Restore Youthful Cellular Activity
The researchers also explored whether physical activity could influence autophagy in older adults.
In a small pilot study, five participants between the ages of 77 and 88 completed a gentle exercise program lasting 12 weeks. The activities focused on reducing the risk of falls, and researchers collected blood samples both before and after the program to measure changes in cellular recycling.
The preliminary results suggested that exercise could lower autophagy activity in blood cells toward levels more typical of younger adults. Participants also showed improvements in physical performance.
Although the pilot involved only five people, the findings raise the possibility that exercise could help regulate cellular recycling in ways that support healthier aging. Larger studies will be needed to establish whether these changes are consistent and how they relate to improvements in physical health.
“It is exciting to have this exercise intervention that may have a positive effect on autophagy and healthy aging, and I’m really excited to see where that goes,” said Kumsta.
Expanding Research Into Exercise and Healthy Aging
The findings highlight the importance of understanding cellular recycling as a process that changes in complex ways throughout life, rather than one that uniformly declines with age. They also suggest that future treatments targeting autophagy may need to account for a person’s age, sex, and the specific cells involved.
To investigate the potential benefits of exercise further, the Kumsta laboratory received a pilot grant from the Altman Clinical and Translational Research Institute at the University of California San Diego (UC San Diego).
The team is now working with the Exercise and Physical Activity Resource Center at UC San Diego on larger studies involving more participants and improved testing methods. These efforts will examine how physical activity affects autophagy, aging, and physical function, with the goal of better understanding whether changes in cellular recycling could eventually contribute to strategies for healthier aging.
Funding: The study was supported by the National Institutes of Health, National Cancer Institute, National Institute on Aging, American Foundation for Aging Research, Conrad Prebys Foundation, The Howard and Maryam Newman Family Foundation, and Leona M. and Harry B. Helmsley Charitable Trust.
Additional authors include:
- Ashley Neil, Alexandre R. Colas, Sanjeev S. Ranade, and Anne G. Bang at Sanford Burnham Prebys.
- Stephanie R. Heimler, Ryan J. Moran, Hava Shoshana Barkai, Lina Scandalis, Larissa Traxler, Stephen Dozier, Jaclyn Bergstrom, Jerome Mertens, David Wing and Anthony J. Molina at the UC San Diego.
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