Study: Reversing aging of skeletal muscle

BUFFALO, N.Y. — A University at Buffalo-led research team has shown that a protein named for the mythical land of youth in Irish folklore is effective at reversing aging in skeletal muscle cells.

Published Sept. 3 in Science Advances, the study centers on the protein NANOG, which is derived from Tír na nÓg, a place in Irish lore renowned for everlasting youth, beauty and health.

In a series of experiments, researchers overexpressed NANOG in myoblasts, which are the embryonic precursors to muscle tissue. The myoblasts were senescent, meaning they were no longer able to divide and grow.

The overexpression ameliorated some of the primary characteristics associated with age-related deterioration of cells, including autophagy, energy homeostasis, genomic stability, nuclear integrity and mitochondrial function.

Most notably, NANOG increased the number of muscle stem cells in the muscle of prematurely aging mice. This demonstrated the feasibility of reversing cellular aging in the body without the need to reprogram cells to an embryonic pluripotent state, a process that’s often used in stem cell therapy but runs the risk of tumorigenesis.

“Our work focuses on understanding the mechanisms of NANOG’s actions in hopes of discovering druggable targets in signaling or metabolic networks that mimic the anti-aging effects of NANOG. Ultimately, the work could help lead to new treatments or therapies that help reverse cellular senescence, and aid the many people suffering from age-related disorders,” says the study’s corresponding author Stelios Andreadis, PhD, SUNY Distinguished Professor in the Department of Chemical and Biological Engineering at the UB School of Engineering and Applied Sciences.

The work was supported by grants from the National Institutes of Health, including the National Institute on Aging; a Veteran Affairs Biomedical Laboratory Research Development grant; and an Indian Trail Charitable Foundation grant.

In addition to Andreadis, study co-authors affiliated with the UB Department of Chemical and Biological Engineering include Aref Shahini, Nika Rajabian, Debanik Choudhury, Shahryar Shahini, Joseph Kulcczyk, Izuagie Ikhapoh and Pedro Lei.

Co-authors affiliated with the UB Department of Biomedical Engineering, a program between UB’s engineering school and the Jacobs School of Medicine and Biomedical Sciences at UB, include Kalyan Vydiam, Thy Nguyen, Tyler Santarelli and Andreadis.

Co-authors affiliated with the Department of Medicine in the Jacobs School are Ramkumar Thiyagarajan, Kenneth Seldeen and Bruce Troen.

Co-authors affiliated with Department of Biostatistics and Bioinformatics at Roswell Park Comprehensive Cancer Center include Yali Zhang, Jianmin Wang, Song Liu. Co-author Aimie Stablewski is affiliated with Roswell Park’s Gene Targeting and Transgenic Shared Resource.

Co-author Jennifer Peirick is affiliated with UB’s Comparative Medicine Laboratory Animal Facilities. Troen is also affiliated with VA Western New York Healthcare System. Additionally, Stelios Andreadis is affiliated with UB’s New York State Center of Excellence in Bioinformatics and Life Sciences, and UB’s Center for Cell Gene and Tissue Engineering.