UB study shows that key protein can slow aging

BUFFALO, N.Y. — The United States is a rapidly aging country. By the year 2050, nearly 1 in 4 Americans will be 65 or older, and many will live into their 90s and beyond. This leads to health care and social support concerns and also begs the question: What is the quality of life in those later years?

Despite advances in medicine and the eradication of many diseases, it’s hard to escape the downfalls of advanced age: lower immunity and increased chronic inflammation, which can result in arthritis, fatigue, weaker bones and decreased strength, among other maladies.

This chronic activation of inflammation associated with aging has been coined “inflammaging,” says Keith Kirkwood, DDS, PhD, senior associate dean for research and Centennial Endowed Chair in the Department of Oral Biology in the University at Buffalo School of Dental Medicine.

“These age-related changes, known as immunosenescence, lead to a decline in immune resilience and an increased susceptibility to age-related chronic inflammatory diseases,” he explains.

Kirkwood recently led a lengthy study looking into a way to decrease age-related frailty in mice. He and his team, which includes two top geriatric experts, focused on tristetraprolin (TTP), an RNA-binding protein that essentially puts the brakes on inflammation. As people age, TTP levels drop, especially in immune cells, leading to more inflammation.

The team genetically manipulated one group of elderly mice so that TTP was stabilized. Their findings — that these mice had reduced physical frailty scores compared with control mice — were published in the January 2026 issue of Aging and Disease.

“This protein really targets RNA for rapid degradation,” says, Kirkwood, who has focused his decades-long research on the role of obesity and aging in myeloid cell biology as it relates to oral inflammation in periodontal disease and oral cancer progression. “Most pro-inflammatory mediators have a very short half-life, meaning they only last for minutes, not hours.”

Funded by a $2.1 million grant from the National Institutes of Health, the study took place over the past six years at both UB’s South and Downtown campuses.

“In the United States, the prevalence of frailty in the non-nursing home population ages 65 and older is about 15%,” Kirkwood says. “Therefore, understanding the mechanisms connecting inflammaging, immune system alterations, bone health and frailty is essential for developing targeted interventions to improve the quality of life in aging populations.”

He created the study with longtime collaborators Bruce Troen, MD, professor and chief of geriatric medicine and director of the Landon Center on Aging at the University of Kansas School of Medicine who previously taught in UB’s Jacobs School of Medicine and Biomedical Sciences, and Perry Blackshear, MD, PhD, a now retired investigator with both the Department of Biochemistry and Medicine at Duke University Medical Center and the Molecular and Cellular Biology Laboratory at the National Institute of Environmental Health Science in the Research Triangle Park.

Postdoctoral researchers and graduate students also contributed to the study. Ramkumar Thiyagarajan, a post-doc who worked for Kirkwood and is now an assistant professor at the University of Kansas, was the first author of the paper.

The mice, which were 22 months old, were tested on grip strength, gait speed, treadmill endurance and energy levels. The frailty score was significantly lower in the male mice with the TTP increase and somewhat lower in the female mice compared with the controls.

“The increase in TTP resulted in better grip strength, better walking, endurance and overall physical performance,” Kirkwood explains. “These mice had healthier bones and reduced bone breakdown. They exhibited a more youthful-looking immune profile.”

Female mice with increased TTP didn’t fare quite as well as their male counterparts. Kirkwood attributes this to their smaller physical size and estrogen declines, which may restrict tissue responsiveness to anti-inflammatory modulation. However, he says that both sexes with the enhanced TTP expression had stronger bones.

While this study shows amazing results in mice, Kirkwood points out that clinical trials for humans are a long way off. Blackshear has carried out preliminary drug screening efforts to look for compounds that might boost TTP expression but none has shown clear success to date.

“We would like to close that gap in the future,” Kirkwood says, adding that this study does indicate that some manipulation of TTP could help humans and other animals with further research.

In the more immediate future, Kirkwood plans to collaborate with Thiyagarajan on a study of how TTP can control the neuroinflammation associated with aging, such as dementia and Alzheimer's disease.

“I’m optimistic about where this research could lead and what we may learn as studies continue over time,” Kirkwood says.