Boosting Protein Tristetraprolin Improves Strength in Aging Mice

Researchers at the University at Buffalo have identified a potential pathway to combatting age-related decline by enhancing a specific protein. In a study published in the January 2026 issue of Aging and Disease, scientists genetically modified elderly mice to increase levels of the protein tristetraprolin (TTP), observing significant improvements in their physical health and resilience.

TTP is an RNA-binding protein that plays a crucial role in regulating inflammation by degrading inflammatory signals. As individuals age, TTP levels naturally decrease, a phenomenon that contributes to a chronic, low-grade inflammation known as "inflammaging." This sustained inflammation gradually damages tissues and weakens the body, leading to immunosenescence, a decline in immune function, and increased susceptibility to age-related diseases. Dr. Keith Kirkwood, senior associate dean for research and Centennial Endowed Chair in the Department of Oral Biology at the University at Buffalo School of Dental Medicine, explained that this age-related decline in TTP can allow inflammation to become more widespread.

The six-year study, supported by a $2.1 million grant from the National Institutes of Health, involved elderly mice aged 22 months. By ensuring TTP remained stable in a group of these mice, the research team aimed to see if restoring its levels could mitigate age-related health issues. "This protein really targets RNA for rapid degradation," Dr. Kirkwood stated. "Most pro-inflammatory mediators have a very short half-life, meaning they only last for minutes, not hours." The findings indicated that boosting TTP levels in male mice significantly reduced frailty scores compared to their untreated counterparts.

Physical Performance and Bone Health Enhancements

The improvements observed in the mice were multifaceted. Enhanced TTP levels led to better grip strength, improved walking speed, increased treadmill endurance, and overall enhanced physical performance. Beyond muscle function, the mice with higher TTP also exhibited healthier bones and reduced bone breakdown, presenting a more youthful immune profile. While female mice showed some benefits, their response was less pronounced than that of males. Dr. Kirkwood suggested this difference might be linked to their smaller body size and declining estrogen levels, which could influence tissue response to anti-inflammatory changes. Nevertheless, both sexes demonstrated stronger bones when TTP expression was bolstered.

Frailty is a significant concern in aging populations. In the United States, approximately 15% of individuals aged 65 and older, excluding those in nursing homes, experience frailty. Understanding the intricate connections between inflammaging, immune system alterations, bone health, and frailty is therefore essential for developing effective interventions. Dr. Kirkwood collaborated on the study with Dr. Bruce Troen from the University of Kansas School of Medicine and Dr. Perry Blackshear, a former investigator with Duke University Medical Center and the National Institute of Environmental Health Science. Ramkumar Thiyagarajan, now an assistant professor at the University of Kansas, was the paper's first author.

While these findings offer a promising glimpse into potential strategies for healthier aging, Dr. Kirkwood cautioned that human treatments are still a distant prospect. Early drug screening efforts by Dr. Blackshear to identify compounds that could increase TTP expression have not yet yielded definitive success. The team is now planning further studies to explore whether manipulating TTP could also help mitigate neuroinflammation associated with aging disorders like 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 concluded, expressing hope that this line of inquiry could eventually benefit both humans and other animals.