Incredible protein can reverse muscle aging, new research finds
[Nov. 15, 2022: Cory Nealon, University at Buffalo]
Research team has shown that a protein can reverse aging in skeletal muscle cells. (CREDIT: Creative Commons)
Cellular senescence due to aging or chronic disease impedes stem cell function and regeneration. Skeletal muscle is a highly regenerative organ that comprises ~45% of body mass and enables skeletal movements while also regulating metabolism.
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 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 research could help lead to treatments for atherosclerosis, osteoporosis and other age-related disorders (Credit: University of Buffalo)
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.
This illustration shows a senescent muscle cell (left), including the numerous factors that led to its declining ability to divide and grow. It also shows the same type of cell after the overexpression of NANOG, which reversed many of the factors. (CREDIT: University at Buffalo)
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.
Representative picture of a heterozygous LAKI progeria mouse (LmnaG609G/+) and his WT sibling (Lmna+/+) both at the age of 10 months. (CREDIT: Science Advances Research Article)
“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.
Fluorescent confocal image of NANOG Polyclonal Antibody. (CREDIT: Abcepta)
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 T. Andreadis, PhD, SUNY Distinguished Professor in the Department of Chemical and Biological Engineering at the UB School of Engineering and Applied Sciences.
What is cellular senescence?
Senescent cells are unique in that they eventually stop multiplying but don’t die off when they should. They instead remain and continue to release chemicals that can trigger inflammation. Like the one moldy piece of fruit that corrupts the entire bowl, a relatively small number of senescent cells can persist and spread inflammation that can damage neighboring cells.
However, not all senescent cells are bad. The molecules and compounds expressed by senescent cells (known as the senescent secretome) play important roles across the lifespan, including in embryonic development, childbirth, and wound healing.
How cellular senescence affects the body
The number of senescent cells in a person’s body increases with age. As the aging immune system becomes less efficient, senescent cells accumulate and taint healthy cells. This can affect a person’s ability to withstand stress or illness; recuperate from injuries; and learn new things, since senescent cells in the brain can degrade cognitive functions.
As a result, cellular senescence has been connected to a multitude of age-related conditions, including cancer, diabetes, osteoporosis, cardiovascular disease, stroke, Alzheimer’s disease and related dementias, and osteoarthritis. It has also been linked to declines in eyesight, mobility, and thinking ability.
Investigations are underway to see if senescent skin cells may contribute to sagging and wrinkling, and if senescent cells might also be connected to the cytokine storm of inflammation that makes COVID-19 so deadly for older adults.
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Note: Materials provided above by University at Buffalo. Content may be edited for style and length.
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