Telomerase Protects Against Chronic Disease Beyond Cellular Aging

A protein long studied for its connection to aging may also play a key role in protecting the body from chronic disease, according to new research from the laboratory of Mikhail Kolonin, PhD, published in Aging Cell.

Telomerase is a protein best known for maintaining the protective caps on chromosomes called telomeres. For years, telomerase has been associated with slowing cellular aging by preserving telomeres, which naturally shorten over time. Telomerase is known to play a critical role in keeping cells healthy and helping to protect the body from inflammation, metabolic disease, and organ damage.

But growing evidence suggests the protein has additional, less understood functions. This new work focuses on immune cells known as myeloid cells, which include macrophages-key players in inflammation and tissue health."

Mikhail Kolonin, PhD, UTHealth Houston

Using genetically engineered murine models lacking telomerase specifically in these immune cells, the researchers revealed striking changes. Macrophages developed signs of premature cellular aging despite having normal telomere length. Notably, they became more inflammatory and accumulated lipids, transforming into so-called "foam cells"-a hallmark of conditions like atherosclerosis.

"These findings reveal new mechanisms of cellular aging and the diseases that come with it," Kolonin said. "They show that telomerase is doing much more than maintaining telomeres: it directly influences how immune cells behave and contribute to disease."

The consequences for overall health were significant. When fed a high-calorie diet, models without telomerase in myeloid cells displayed increased body fat, impaired glucose metabolism, abnormal lipid handling, and low-grade fever. Importantly, even on normal diet, these models developed lung scarring (pulmonary fibrosis) and signs of cardiac dysfunction.

This research builds on earlier findings linking telomerase to the prevention of cellular senescence in multiple cell types. Expanding its role to the immune system offers new insight into how aging processes contribute to disease. Together, these findings point to a function of telomerase in mitochondria, the cell's "batteries", which maintain tissues energized and functional.

According to Kolonin, this work, uncovering non-canonical function of telomerase, opens new avenues for therapies aimed at reducing inflammation and treating conditions such as metabolic disorders, fibrosis, and cardiovascular disease.

While more research is needed to determine how these findings translate to humans, the work provides a compelling new perspective on the biology of aging-and suggests that targeting telomerase pathways in immune cells could one day help combat multiple chronic diseases at once.

Kolonin is professor and Harry E. Bovay, Jr. Distinguished University Chair in Metabolic Disease Research at the UTHealth Houston Institute of Molecular Medicine's Center for Metabolic and Degenerative Diseases. Co-authors from McGovern Medical School are Zhanguo Gao, PhD, senior research scientist; Yongmei Yu, research associate, David Wiggins, research, and Eva Sevick-Muraca, PhD, professor. The research is supported by the Harry E. Bovay, Jr. Foundation, Levy-Longenbaugh Fund, and the National Institutes of Health.