Improvements in public health have allowed humanity to reach unprecedented ages, yet for many, these additional years are not spent in optimal health. Aging, while a natural part of life, is closely linked with a rise in chronic diseases such as cancer, diabetes, and Alzheimer’s. The laboratory of Kris Burkewitz, assistant professor of cell and developmental biology, is investigating how to decouple aging from disease, aiming to extend healthy lifespan.
Burkewitz’s team focuses on the organization of cellular compartments, or organelles, and how their structures influence cellular function, metabolism, and disease risk. In a recent paper published in Nature Cell Biology, Burkewitz reveals a novel adaptation mechanism in aging cells: the remodeling of the endoplasmic reticulum (ER), a major cellular organelle, through a process called ER-phagy.
The Discovery of ER-Phagy
ER-phagy selectively targets specific ER subdomains for breakdown, a process now identified as crucial in the aging mechanism. This discovery positions ER-phagy as a potential target for drugs aimed at treating age-related conditions, including neurodegenerative and metabolic diseases.
“Where many prior studies have documented how the levels of different cellular machineries change with age, we are focusing instead on how aging affects the way that cells house and organize these machineries within their complex inner architectures,” Burkewitz explained.
To illustrate, Burkewitz likens a cell to a factory requiring specialized machinery. “Even if all the machinery is present, the factory only runs smoothly if they are arranged correctly,” he said. “If organization breaks down, production becomes inefficient.”
Breakthrough in Aging Research
The study, led by Eric Donahue, PhD’25, utilized advanced genetic tools and microscopy to observe ER structures in Caenorhabditis elegans worms, a model organism for aging research. These worms, transparent and rapidly aging, allow researchers to observe cellular changes in real-time.
Findings revealed that aging cells reduce “rough” ER, involved in protein production, while “tubular” ER, linked to lipid production, remains largely unchanged. This aligns with known aging patterns, such as decreased protein maintenance and altered fat metabolism.
“We didn’t just add a piece to the aging puzzle—we found a whole section that hasn’t even been touched,” said Donahue, highlighting the significance of their findings.
Future Directions in Aging Research
The Burkewitz lab plans to further explore ER structures and their impact on cellular metabolism. As the ER orchestrates the organization of cellular components, understanding its remodeling could illuminate early aging triggers leading to dysfunction and disease.
“Changes in the ER occur relatively early in the aging process,” Burkewitz noted. “One of the most exciting implications is that it may be one of the triggers for what comes later: dysfunction and disease.”
Identifying these triggers could pave the way for interventions to halt or reverse the aging process, offering hope for a healthier, longer life.
Collaborative Efforts and Funding
This groundbreaking research was conducted in collaboration with Vanderbilt University labs and partners from the University of Michigan and the University of California, San Diego. It was funded by the National Institute on Aging, the National Institute of General Medical Sciences, and the Glenn Foundation for Medical Research/American Federation for Aging Research.
The paper, titled “ER remodeling is a feature of aging and depends on ER-phagy,” was published in February 2026 in Nature Cell Biology.
As scientists continue to unravel the complexities of aging, this discovery marks a significant step towards understanding and potentially mitigating age-related diseases, underscoring the profound impact of cellular architecture on health and longevity.
