A Single Protein Could Determine How Well We Age
Older mice engineered to maintain higher levels of an inflammation-suppressing protein demonstrated stronger grip, faster walking speed, and greater stamina than untreated animals, according to research from the University at Buffalo.
The findings, published this month in Aging and Disease, indicate that preserving this molecular brake on inflammation could meaningfully slow the physical decline associated with aging.
What Is TTP?
The protein at the center of this discovery is called tristetraprolin (TTP). Under normal circumstances, TTP functions as a cleanup crew for inflammatory signals, marking them for rapid destruction so they do not accumulate in the body.
However, as people age, TTP levels decline—particularly within immune cells. When TTP becomes insufficient, inflammatory activity rises unchecked. Researchers have termed this persistent, low-grade inflammation "inflammaging".
This age-related shift weakens immune resilience and increases vulnerability to chronic inflammatory conditions, according to the research team.
The Study Design
The research team sought to determine what would occur if they prevented TTP levels from falling. Using older mice equivalent to late-life humans, investigators stabilized TTP so it would not diminish with age.
Grip Strength
The mice underwent grip strength testing to measure muscular function.
Walking Speed
Walking speed trials assessed mobility and coordination.
Endurance
Treadmill endurance tests evaluated overall stamina and cardiovascular fitness.
Health Markers
Bone density and immune cell health were examined to determine broader physiological impacts.
The results proved striking. Male mice with elevated TTP scored significantly better across all performance measures. Their bones remained healthier, and their immune cells bore characteristics more typical of younger animals.
Research Context
The study spanned six years and received $2.1 million in funding from the National Institutes of Health. Keith Kirkwood, senior associate dean for research at the university's School of Dental Medicine and the study's lead investigator, collaborated with Bruce Troen from the University of Kansas and Perry Blackshear, formerly affiliated with Duke University Medical Center and the National Institute of Environmental Health Sciences.
Kirkwood noted that TTP specifically targets RNA for rapid degradation. Most pro-inflammatory mediators have very short half-lives, persisting for minutes rather than hours.
Sex-Based Differences
Female mice also showed improvement, though the gains were less pronounced than those observed in males.
Researchers suspect that lower body weight and declining estrogen levels in aging females may limit how tissues respond to TTP-driven anti-inflammatory signals. Despite this variation, bone strength improved across both sexes.
Looking Ahead
Translating these mouse findings into human treatments remains a distant objective. Blackshear has begun preliminary drug screening to identify compounds capable of boosting TTP activity, though no promising candidates have emerged yet.
The team is also investigating whether TTP stabilization might address neuroinflammation associated with conditions such as dementia and Alzheimer's disease.
Nearly one-quarter of Americans are projected to be over 65 by 2050, with roughly 15 percent of that age group currently experiencing frailty. Finding ways to delay or reduce that decline carries substantial implications for both individuals and health systems.
The researchers expressed optimism about the direction of this work and its potential to influence healthy aging interventions in the future.
Based on: A Single Protein Could Determine How Well We Age; University at Buffalo; Aging and Disease, 2024.