A $1 million grant will fund aging research at Pitt

The University of Pittsburgh received $1 million from the Richard King Mellon Foundation to support four projects that advance new and ongoing translational research on aging. These studies have the potential to create novel products and technologies for commercial investment to improve health outcomes and reduce the burden of age-related problems.

New treatments for age-related diseases, such as diabetes and Alzheimer’s, are urgently needed — nearly 25% of people in the United States will be 65 or older by 2060.

The foundation believes finding interventions that slow aging “would challenge the notion that our quality of life is likely to decline beginning at a certain age.”

“Investigating disorders of aging, such as dementia and cardiovascular disease, and identifying therapies to disrupt the process will lead to better quality of life for all of us,” said Anantha Shekhar, senior vice chancellor for the health sciences and John and Gertrude Petersen Dean of the School of Medicine at Pitt. “The grants from the Richard King Mellon Foundation will help accelerate our efforts in these important areas.”

Grants were made to:

• Launch a project to reverse organ aging. Researchers will explore the role of a compound that blocks the enzyme purine nucleoside phosphorylase (PNPase), which is associated with cell damage. The new project will build upon preliminary work suggesting that blocking PNPase can reverse age-related damage in multiple organ tissues. This research is led by Lori Birder, professor of medicine in Pitt’s Division of Renal-Electrolyte.
• Explore the importance of nuclear speckles. These drop-like subnuclear organelles are key to manufacturing proteins. The project will evaluate ways to “rejuvenate” nuclear speckles using drugs or gene therapy. These approaches may help restore the healthy balance of proteins within cells, thereby possibly delaying, or even reversing, aging. This project is led by Bokai Zhu, assistant professor of medicine in Pitt’s Division of Endocrinology and Metabolism.
• Develop a drug that boosts the activity of a protein, NAD+. This protein, which declines during aging, is key to energy metabolism and influences other fundamental biological processes, including stress response. The research aims to identify a compound that elevates NAD+ levels and at the same time penetrates the central nervous system. This feature could enable the newly identified agent to improve cognition in Alzheimer’s disease patients and those with other age-related diseases driven by NAD+ decline. These investigations are led by Yuan Liu, assistant professor of medicine in Pitt’s Division of Pulmonary, Allergy, and Critical Care Medicine.
• Research and develop a potential strategy for anti-aging in late life. This work will target a combination of key factors, including cell nutrient sensing, gene regulation and cell senescence, which is when cells stop multiplying. The team will evaluate whether targeting these multiple processes later in life will have an additive, or even synergistic, effect in delaying or reversing aging. The research is led by Andrey Parkhitko, assistant professor of medicine in Pitt’s Division of Endocrinology and Metabolism.

These latest awards follow $750,000 in grants made by the Richard King Mellon Foundation in fall 2022 to Pitt faculty pursuing aging-related studies. The three earlier research projects focus on developing a tool to identify “zombie” cells that secrete tissue-damaging chemicals, the use of melatonin to reduce cognitive decline and a tool to investigate the relationship between aging and damage to telomeres, which are the ends of chromosomes.

Five of the seven total awards went to faculty in the Aging Institute, which has a mission to understand how — and why — we age and to leverage this information for new therapies to treat age-related diseases.