Connecting Aging Cells to Muscle Decline

What biomedical issue did you address in your research, and what did your studies find?

My research focused on understanding how inflammation and cellular senescence contribute to muscle decline with aging. Cellular senescence is a state in which cells stop dividing but continue to release inflammatory signals. As people age, senescent cells may contribute to chronic, low-level inflammation, often referred to as "inflammaging," which can affect metabolism, muscle health and physical function.

I analyzed clinical samples, including muscle and fat tissue biopsies, from young adults and older adults. I found that, compared with younger individuals, older adults had higher levels of senescence in both fat tissue and skeletal muscle, measured by the expression of two senescence-associated genes, CDKN1A and CDKN2A. Older adults also had higher levels of inflammatory factors in circulation. In fat tissue, these senescence markers were associated with greater inflammation and higher fat mass. They were also linked to lower insulin sensitivity and decreased aerobic fitness. In skeletal muscle, CDKN1A was associated with reduced mitochondrial function and lower muscle power.

Together, these findings suggest that senescent cells in fat and muscle tissue may play an important role in age-related muscle decline.

What aspects of your training at Mayo helped you grow as a scientist and as a thinker?

My appreciation for the power of collaboration grew during my time at Mayo Clinic. Throughout my graduate training, I saw how many different perspectives and areas of expertise can come together to shape a set of data into a meaningful scientific story.

Throughout my dissertation, I was able to take advantage of several Mayo Clinic research resources and core facilities, including the Genome Analysis Core, Targeted Biomarker Core, Metabolomics Core and Flow Cytometry Core. These resources allowed me to gain valuable experience with clinical research, human tissue processing and experimental approaches that connected basic science with patient-centered questions.

Mayo's environment also encouraged me to seek out perspectives beyond my own field. Being surrounded by clinicians, basic scientists and translational researchers challenged me to think more broadly and helped expand my understanding of what biomedical research can accomplish.

What's next?

I will continue pursuing my M.D. degree at the University of Puerto Rico School of Medicine. My goal is to become a pathologist-scientist and use the research skills I developed during my Ph.D. training at Mayo to address unanswered clinical questions.

My advice to students considering a doctoral degree in biomedical sciences is to think about how the training fits their long-term goals. For me, the Ph.D. was the right fit because I wanted rigorous research training that would prepare me to develop independent research questions and eventually lead my own projects as a physician-scientist.

This article was written by Meredith Lilley, a Ph.D. candidate in Neuroscience at Mayo Clinic Graduate School of Biomedical Sciences.