Researchers at the University at Buffalo have identified a protein that, when enhanced in aging mice, restored their strength, improved bone health, and sharpened their immune function. The discovery points to a potential new avenue for combating the physical deterioration that accompanies growing old.
The protein is tristetraprolin, or TTP, which acts as a molecular bouncer in the body. It intercepts and destroys inflammatory signals before they can accumulate and damage tissues. As people age, TTP levels naturally plummet, particularly in immune cells, leaving inflammation unchecked.
Keith Kirkwood, a senior researcher at UB's School of Dental Medicine, calls this creeping inflammation "inflammaging." It is a constant, low-level state of inflammation that gradually weakens the body's defenses and accelerates decay. The phenomenon drives immunosenescence, the age-related collapse of immune resilience that makes older people more vulnerable to chronic disease.
To test whether restoring TTP could reverse this decline, Kirkwood's team genetically modified elderly mice to stabilize the protein. The mice were 22 months old, equivalent to advanced age in rodent terms. The researchers measured their grip strength, walking speed, treadmill endurance, and overall vitality before and after the intervention.
Male mice with elevated TTP showed dramatically lower frailty scores than untreated controls. They walked faster, gripped harder, endured longer on the treadmill, and displayed significantly healthier bones with reduced breakdown. Female mice improved as well, though the gains were more modest, possibly because their smaller body size and declining estrogen limited how much their tissues could respond to the anti-inflammatory boost.
Both sexes developed stronger bones when TTP expression increased. The enhanced mice also exhibited what Kirkwood describes as a "more youthful-looking immune profile," suggesting the intervention reverses some hallmarks of aging at the cellular level.
The findings, published in January 2026 in Aging and Disease, grew from a six-year effort supported by a 2.1 million dollar grant from the National Institutes of Health. Kirkwood collaborated with Bruce Troen, chief of geriatric medicine at the University of Kansas, and Perry Blackshear, a retired investigator from Duke University and the National Institute of Environmental Health Sciences.
The urgency of the work is clear. By 2050, nearly one in four Americans will be 65 or older. About 15 percent of that age group lives with frailty, a condition that undermines independence and quality of life. Understanding how inflammaging, immune breakdown, and bone loss interconnect is essential for developing therapies that could help millions of aging adults stay stronger and healthier.
Still, Kirkwood urges caution. Human treatments remain years or decades away. Perry Blackshear has already begun screening drugs to identify compounds that could boost TTP expression in people, but none have yet shown clear promise. The path from mouse to medicine is long, and there is no guarantee the results will translate.
Kirkwood's team is already eyeing a broader target. Future studies will explore whether ramping up TTP could also dampen neuroinflammation linked to dementia and Alzheimer's disease, conditions that impose an enormous burden on aging populations and their families.
Author Jessica Williams: "This is the kind of foundational research that could reshape how we think about aging, but let's not get ahead of ourselves. A drug that safely boosts TTP in humans would be transformative, but getting from mouse muscles to human medicine is where most promising leads disappear."
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