Researchers at Vanderbilt University have identified a new cellular process that may play a key role in healthy aging. The study, led by Kris Burkewitz, assistant professor of cell and developmental biology, explores how cells organize their internal structures and how these changes impact disease risk as people age.
The research focuses on the endoplasmic reticulum (ER), one of the largest organelles in cells. Burkewitz's team discovered that as cells age, they remodel the ER through a process called ER-phagy, which selectively breaks down certain parts of the ER. This remodeling could be linked to chronic diseases associated with aging, such as neurodegenerative and metabolic disorders.
Burkewitz explained the importance of this process by comparing it to a factory: "When space is limited or production demands change, the factory has to reorganize its layout to make the right products," he said. "If organization breaks down, production becomes very inefficient."
Eric Donahue, PhD'25 and first author of the paper published in Nature Cell Biology, emphasized the significance of their findings: "We didn't just add a piece to the aging puzzle—we found a whole section that hasn't even been touched." Donahue conducted his research using Caenorhabditis elegans worms because they are transparent and age quickly, making them useful for observing cellular changes during aging.
The team observed that older animals showed a significant reduction in "rough" ER—responsible for protein production—while "tubular" ER related to fat production was less affected. These shifts reflect broader patterns seen in aging organisms, such as reduced protein maintenance and altered fat storage.
Further investigation revealed that ER-phagy is not only involved in remodeling but also linked directly to lifespan and healthy aging. The researchers plan to continue studying how changes in ER structure affect other cell components over time.
"Changes in the ER occur relatively early in the aging process," Burkewitz noted. "One of the most exciting implications of this is that it may be one of the triggers for what comes later: dysfunction and disease."
The study was conducted with collaborators from Vanderbilt University’s labs led by Jason MacGurn, Andrew Folkmann, Rafael Arrojo e Drigo, Lauren Jackson; as well as researchers from University of Michigan and University of California San Diego. Funding came from sources including the National Institute on Aging and Glenn Foundation for Medical Research/American Federation for Aging Research.
The full findings are detailed in "ER remodeling is a feature of aging and depends on ER-phagy," published in Nature Cell Biology in February 2026.
