Scientists Identify Protein That Slows Key Effects of Aging

Boosting a protein that suppresses inflammation reduced frailty and improved physical health in aging mice.

The United States is entering a period of rapid population aging. By 2050, nearly one quarter of Americans will be at least 65 years old, and many individuals are expected to live well into their 90s or beyond. This demographic shift raises questions about health care systems and long-term support, but it also prompts a deeper concern about the quality of life people experience as they age.

Even with major advances in modern medicine and the elimination or control of many once-deadly diseases, aging still brings biological challenges. Older adults often experience weaker immune defenses along with persistent low-level inflammation throughout the body. This chronic inflammation is linked to conditions such as arthritis, fatigue, bone loss, and declining muscle strength.

Aging immune systems fuel chronic inflammation

Scientists refer to this persistent inflammatory state that develops with age as “inflammaging,” says Keith Kirkwood, senior associate dean for research and Centennial Endowed Chair in the Department of Oral Biology, 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.

A protein that restrains inflammation

Keith Kirkwood recently led a long-term investigation exploring whether it might be possible to reduce physical frailty associated with aging. The work focused on tristetraprolin (TTP), a protein that binds RNA and plays an important role in regulating inflammation. In healthy conditions, TTP helps limit inflammatory signals, but its levels tend to decline with age, particularly in immune cells. As TTP levels fall, inflammatory activity rises.

To examine the effects of restoring this control mechanism, the research team genetically modified a group of older mice so that TTP remained stable rather than declining with age. Their findings showed that mice with stabilized TTP experienced lower levels of physical frailty compared with untreated animals. These results 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.”

Multi-year study examines aging frailty

Supported by a $2.1 million grant from the National Institutes of Health, the research project unfolded over six years and involved work at both the 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.”

Keith Kirkwood designed the study in collaboration with Bruce Troen, 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, 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.

Additional contributions came from postdoctoral researchers and graduate students. Ramkumar Thiyagarajan, who conducted postdoctoral work with Kirkwood and is now an assistant professor at the University of Kansas, served as the first author of the paper.

Stabilizing TTP reduces frailty in mice

The study involved mice that were 22 months old, an age that corresponds to late life in humans. The animals were evaluated through a series of physical performance tests, including grip strength measurements, walking speed assessments, treadmill endurance trials, and monitoring of energy levels.

Male mice with elevated TTP showed significantly lower frailty scores compared with untreated mice, while female mice also showed improvement, though the change was less pronounced.

“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 did not respond as strongly as the males. Kirkwood attributes this difference partly to smaller body size and declining estrogen levels, which may limit how tissues respond to anti-inflammatory regulation. Even so, enhanced TTP activity improved bone strength in both male and female animals.

Translating findings to human aging

Although the results in mice are encouraging, Keith Kirkwood notes that translating these findings into treatments for humans will take considerable time. Perry Blackshear has already begun early drug screening efforts aimed at identifying compounds that could increase TTP levels, but no candidate molecules have yet shown clear effectiveness.

“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 near term, Keith Kirkwood plans to continue collaborating with Ramkumar Thiyagarajan to investigate how TTP may influence neuroinflammation related to aging conditions 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.

Reference: “Increased Stability of Tristetraprolin mRNA Supports Bone Health and Decreases Frailty During Aging” by Ramkumar Thiyagarajan, Lixia Zhang, Leticia Andrea Rojas Cortez, Kyu Hwan Kwack, Victoria Maglaras, Nanda Kumar Yellapu, Yukitomo Arao, Kenneth L. Seldeen, Perry J. Blackshear, Bruce R. Troen and Keith L. Kirkwood, 13 January 2026, Aging and Disease.
DOI: 10.14336/AD.2025.1243

This work was supported by the National Institutes of Health (NIH) grants, R01DE028258 (KK), K18DE 029526 (KK), K07AG060266 (BT), K12DE 027826 (VM), BX004369 (BT), and the Indian Trail Foundation (BT) and by the Intramural Research Program of the National Institutes of Health (NIH).

Never miss a breakthrough: Join the SciTechDaily newsletter.
Follow us on Google and Google News.