As the U.S. population ages, scientists are looking for ways to help people stay healthy later in life. By 2050, nearly one in four Americans will be over the age of 65, with many expected to live into their 90s. Although modern medicine has dramatically extended lifespans, aging still poses serious physical challenges, including weakened immunity, chronic inflammation, bone loss, fatigue, and decreased physical strength.
Researchers at the University at Buffalo think they may have found an important clue to slowing down some of the changes associated with aging.
Scientists target ‘inflammation’
Aging is often accompanied by an ongoing low-level inflammatory state that gradually damages tissues and weakens the body. Scientists call this process “inflammation,” according to Dr. Keith Kirkwood, senior associate dean and Centennial Endowed Chair in Oral Biology at Buffalo School of Dentistry.
“These age-related changes, known as immunosenescence, lead to decreased immune resilience and increased susceptibility to age-related chronic inflammatory diseases,” Professor Kirkwood explains.
Professor Kirkwood recently led a long-term study focused on reducing frailty in older mice. The study focused on tristetraproline (TTP), an RNA-binding protein that helps control inflammation by destroying inflammatory signals before they can build up.
As we age, TTP levels naturally decrease, especially in immune cells. This drop can cause inflammation to spread further throughout the body.
Improve muscle strength and bone health with a protein boost
To investigate whether restoring TTP could improve age-related health problems, the researchers genetically engineered a group of older mice so that the protein remained stable. Their findings were published in the January 2026 issue of the journal. aging and disease.
“This protein actually targets RNA and degrades it rapidly,” says Professor Kirkwood, who has spent decades studying obesity, aging, oral inflammation, periodontal disease and the development of oral cancer. “Most pro-inflammatory mediators have very short half-lives, lasting only minutes instead of hours.”
The project was supported by a $2.1 million grant from the National Institutes of Health and was conducted over six years at UB’s South and Downtown campuses.
“In the United States, the prevalence of frailty in the non-nursing facility population aged 65 and older is approximately 15%,” Kirkwood says. “Understanding the mechanisms linking inflammation, immune system changes, bone health, and frailty is therefore essential to developing targeted interventions to improve quality of life in aging populations.”
Professor Kirkwood worked on this study with longtime collaborators Bruce Troen, MD, PhD, professor and director of geriatric medicine at the University of Kansas School of Medicine and director of the Landon Center on Aging, and Perry Blackshear, MD, former research associate at Duke University Medical Center and the National Institute of Environmental Health Sciences at Research Triangle Park.
Postdoctoral researchers and graduate students also contributed to the project. Ramkumar Thiyagarajan, a former postdoctoral fellow in Kirkwood’s lab and now an assistant professor at the University of Kansas, was the paper’s first author.
Aging mice became stronger and more resilient
The mice that participated in the study were 22 months old, which is considered old for a mouse. The researchers evaluated them using several measures, including grip strength, walking speed, treadmill endurance, and overall energy level.
Male mice with elevated TTP levels showed significantly lower frailty scores than untreated mice. Female mice also showed improvement, but the magnitude of the change was smaller.
“Increasing TTP improved grip strength, gait, endurance, and overall physical performance,” Kirkwood explains. “These mice had healthier bones and less bone destruction. They showed a more youthful immune profile.”
Female mice with higher TTP levels did not respond as strongly as males. Kirkwood says this may be related to their smaller size and lower estrogen levels, which may limit the tissue’s response to changes in anti-inflammatory properties. Still, when TTP expression was enhanced, both male and female mice developed stronger bones.
Human treatment is still far away
Although the findings were encouraging, Kirkwood cautioned that a cure for people is still a long way off. Blackshear has already conducted initial drug screening efforts to identify compounds that can increase TTP expression, but none have yet achieved clear success.
“We hope to close that gap in the future,” Kirkwood said, adding that the results suggest that manipulating TTP could ultimately benefit humans and other animals.
The research team is currently planning additional studies to focus on whether TTP can also help reduce neuroinflammation associated with age-related diseases such as dementia and Alzheimer’s disease.
“I’m optimistic about where this research could lead and what we can learn as it progresses over time,” Kirkwood says.
