Fighting “Inflammaging”: How a Specific Protein Could Slow Age-Related Decline
As the U.S. Population ages, the focus of medical research is shifting from simply extending lifespan to improving “healthspan”—the period of life spent in excellent health. By 2050, nearly one in four Americans will be 65 or older, with many living into their 90s. However, longevity often comes with physical tolls, including declining strength, bone loss, and a weakened immune system.
Researchers at the University at Buffalo believe they’ve identified a critical biological lever that could slow these changes. By targeting a process known as “inflammaging,” scientists are exploring how to maintain physical resilience and bone health well into old age.
- Inflammaging is a chronic, low-level state of inflammation that damages tissues as we age.
- The protein tristetraprolin (TTP) acts as a regulator that breaks down inflammatory signals.
- In elderly mice, stabilizing TTP levels improved grip strength, walking speed, and bone density.
- While promising, human treatments are still in the early stages of development.
Understanding Inflammaging and Immunosenescence
Aging isn’t just about the wear and tear of organs; it’s also about how the immune system evolves. According to Keith Kirkwood, DDS, PhD, senior associate dean for research at the University at Buffalo School of Dental Medicine, aging is often accompanied by a constant, low-level state of inflammation called “inflammaging.”
“These age-related changes, known as immunosenescence, lead to a decline in immune resilience and an increased susceptibility to age-related chronic inflammatory diseases,” Kirkwood explains.
A key player in managing this process is tristetraprolin (TTP), an RNA binding protein. TTP functions as a biological cleanup crew, breaking down inflammatory signals before they can accumulate and cause systemic damage. As people age, TTP levels naturally drop, particularly within immune cells, which may allow inflammation to spread unchecked throughout the body.
The Breakthrough: Restoring TTP in Elderly Models
To see if restoring this protein could reverse age-related decline, a research team—supported by a $2.1 million National Institutes of Health (NIH) grant—conducted a six-year study. They genetically modified elderly mice (22 months old) to ensure their TTP levels remained stable.
The results, published in the January 2026 issue of Aging and Disease, showed significant physical improvements. Researchers measured the mice using treadmill endurance, walking speed, energy levels, and grip strength.
Physical and Structural Gains
The study found that male mice with increased TTP levels had significantly lower frailty scores than untreated mice. Kirkwood notes that “the increase in TTP resulted in better grip strength, better walking, endurance and overall physical performance.”
Beyond muscle strength, the protein had a profound effect on skeletal health. The treated mice exhibited healthier bones and a reduction in bone breakdown, alongside an immune profile that appeared more youthful.
Gender Differences in Response
Interestingly, female mice did not respond as strongly as males, though they still developed stronger bones. Kirkwood suggests this disparity may be linked to smaller body size and declining estrogen levels, which might limit how tissues respond to anti-inflammatory changes.
From Mice to Humans: The Road Ahead
While the results in mice are encouraging, the transition to human medicine is complex. The study was a collaborative effort involving Bruce Troen, MD, from the University of Kansas School of Medicine, and Perry Blackshear, MD, PhD, formerly of Duke University Medical Center and the National Institute of Environmental Health Science. First author Ramkumar Thiyagarajan, now an assistant professor at the University of Kansas, also contributed heavily to the findings.
Currently, human treatments are not yet available. Perry Blackshear has conducted early drug screening to find compounds that can increase TTP expression in humans, but these efforts have not yet produced a clear success. “We would like to close that gap in the future,” says Kirkwood.
Expanding the Research
The team isn’t stopping at physical frailty. They are now planning studies to determine if manipulating TTP can reduce neuroinflammation. This could lead to new interventions for age-related cognitive disorders, including Alzheimer’s disease and dementia.
Why This Matters for Public Health
The drive to understand TTP is rooted in a pressing public health need. Kirkwood points out that approximately 15% of the non-nursing home population aged 65 and older in the U.S. Suffers from frailty. By uncovering the mechanisms that connect inflammaging to bone health and immune dysfunction, researchers hope to develop targeted therapies that don’t just add years to life, but quality to those years.
“I’m optimistic about where this research could lead and what we may learn as studies continue over time,” Kirkwood concludes.
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