Taking out the trash is a chore that even our cells cannot escape. Through a process known as autophagy, they place misshapen proteins and other cellular garbage in biological containers in order to digest them into their molecular building blocks.
Autophagy is designed to prevent the buildup of waste that causes cellular damage. A decline in this cellular recycling procedure is considered one of the hallmarks of aging and is associated with many age-related diseases, including cancer, cardiovascular disease, diabetes and neurodegeneration.
Scientists at Sanford Burnham Prebys Medical Discovery Institute published findings September 27, 2026, in Aging Cell adding new wrinkles to our understanding of the links between aging and autophagy. The study showed that autophagy rates do not simply decline with age but instead vary in different types of cells and based on the sex of research participants. The researchers also show that exercise may modify autophagy levels in humans.
"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."
To conduct their experiments, the research team acquired skin and blood samples from a group of volunteers aged 23 to 72 who self-reported that they had no chronic diseases. The scientists expanded the number of cell types in their study by transforming skin cells into induced neurons.
For each cell type, the investigators sequenced the RNA transcripts created as DNA is "read" to produce proteins, enzymes and other biological machinery. Analyzing these transcripts provided evidence of how age and cell type influenced the expression of autophagy genes that govern cellular recycling. The researchers also used a technique to directly measure the rate of autophagy in cells, enabling them to compare how much autophagy actually occurred to how much would be expected based on gene expression.
"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."
Autophagy declined with age in tests of male skin cells, remained stable in female skin cells and increased in female induced neurons. The research team also found that higher or lower expression levels of autophagy genes were not correlated with the direct measurement of cell recycling rapidity.
"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.
Next, the scientists wanted to test for a potential connection between levels of autophagy and physical function as we age. Their results suggest that elevated autophagy may mean different things in younger and older adults.
Among adults aged 70 and older, higher autophagy was associated with poorer physical function across the three cell types. Increased autophagy in blood cells was associated with decreased aerobic fitness, increased autophagy in skin cells was linked to higher body mass index (BMI), and in induced neurons with lower grip strength and metabolism, and higher resting heart rate.
"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."
In a pilot test of one potential future intervention strategy, the research team looked at the effects of exercise on cellular recycling rates in blood cells of older adults. Five participants aged 77-88 provided blood samples before and after completing a 12-week mild exercise program focused on preventing falls. The results suggest that exercise may reduce blood cell autophagic activity to match more youthful levels while improving physical performance in older adults.
"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.
The Kumsta lab received a pilot grant from the Altman Clinical and Translational Research Institute at the University of California San Diego (UC San Diego) to expand research on this exercise approach for aging, autophagy and physical function. Larger studies with more participants and improved testing protocols are underway in collaboration with the Exercise and Physical Activity Resource Center at UC San Diego.
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
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.
The study's DOI is 10.1111/acel.70734 .
