Alpha ketoglutarate, or AKG, has long been used as a dietary supplement in the bodybuilding world.

By satisfying bioenergetic demands, generating biomass, and providing metabolites serving as cofactors for chromatin modifiers, metabolism regulates adult stem cell biology. Here, we report that a branch of glycolysis, the serine biosynthesis pathway (SBP), is activated in regenerating muscle stem cells (MuSCs). Gene inactivation and metabolomics revealed that Psat1, one of the three SBP enzymes, controls MuSC activation and expansion of myogenic progenitors through production of the metabolite α-ketoglutarate (α-KG) and α-KG-generated glutamine. Psat1 ablation resulted in defective expansion of MuSCs and impaired regeneration. Psat1, α-KG, and glutamine were reduced in MuSCs of old mice. α-KG or glutamine re-established appropriate muscle regeneration of adult conditional Psat1 ^-/- mice and of old mice. These findings contribute insights into the metabolic role of Psat1 during muscle regeneration and suggest α-KG and glutamine as potential therapeutic interventions to ameliorate muscle regeneration during aging.

Keywords: aging; glutamine; ketoglutarate; muscle regeneration; muscle stem cells.

Published by cold spring harbor laboratory press.

Older people may be at greater risk of developing pancreatic cancer and have poorer prognoses because of age-related changes in cells in the pancreas called fibroblasts, according to research led by investigators from the Johns Hopkins Kimmel Cancer Center, the Johns Hopkins Bloomberg School of Public Health and the Bloomberg~Kimmel Institute for Cancer Immunotherapy.

The study, published online Feb. 8 in Cancer Research, provides clues as to why pancreatic cancer is more common and aggressive in older people. It may also help scientists develop new therapeutic approaches for this difficult-to-treat cancer. The study showed that aging alters fibroblasts in ways that enable them to promote pancreatic cancer tumor growth.

“Older fibroblasts release proteins that directly affect pancreatic cancer cells and ultimately lead to the growth and spread of pancreatic cancer tumors,” says the study’s lead author, Daniel Zabransky, M.D., Ph.D., assistant professor of oncology at the Johns Hopkins University School of Medicine. “The younger fibroblasts did not have these capabilities. We think this is a key reason why we see pancreatic cancer more commonly in older patients.”