Researchers at La Jolla’s Sanford Burnham Prebys Medical Discovery Institute say they’ve found the molecular process that prevents muscular generation in older adults.
“In adult skeletal muscle, the process of generating muscle — myogenesis — depends on activating (muscle stem cells) that are in a resting, or quiescent, state,” said Dr. Lorenzo Puri, a professor in the Development, Aging and Regeneration program at SBP.
“As we age, our (muscle stem cells) transition to a permanently inactive state called `senescence,’ from which they can’t be woken up to form new muscle fibers,” Puri said. “If we could encourage senescent (muscle stem cells) to start replicating and advance through myogenesis — perhaps through pharmacological interventions — we may have a way to help build muscle in patients that need it.”
His team found that the muscle cells spontaneously activate a DNA damage response that inhibits them from dividing. Cell division is needed to form new muscle.
The scientists came up with some experimental ways to get senescent cells to move through the cell division cycle and activate myogenesis.
However, they also learned that forcing old muscle stem cells to divide to create new muscle could lead to the formation of myofibers with nuclear abnormalities — the result of genomic alterations during aging.
According to Puri, the study findings “should warn against over- enthusiasm for strategies aimed at rejuvenating muscle of elderly individuals by enforcing the regeneration process, as they might carry a sort of trade- off.”
The risk could be genomic and possibly functional integrity of the newly formed muscles, he said.
Lucia Latella of Italy also participated in the study, which was funded by the National Institutes of Health; Ellison Medical Foundation of Maryland; the Italian Ministry of Education, University and Research and National Research Council; and the Glenn Foundation for Medical Research, based in Santa Barbara and Phoenix.
—City News Service
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