In a study published in the Journal of Gerontology: Biological Sciences, researchers tested 24-month-old rats fed 35% less food for eight weeks. They measured protein phosphorylation, a chemical modification that alters protein activity, and insulin-stimulated glucose uptake by skeletal muscle to understand how calorie restriction affects insulin sensitivity in aging muscle.
Calorie restriction improved insulin-stimulated glucose uptake in both sexes, yet females showed greater uptake than males regardless of diet. At the molecular level, insulin altered phosphorylation on more than twice as many protein sites in females than in males, with 60 sites changed in both sexes. Conversely, calorie restriction altered phosphorylation on about 30% more protein sites in males than in females. The authors interpret these differences to mean males and females use different molecular strategies to reach a similar functional outcome: better muscle sugar metabolism.
The study also identified two proteins, Lmod1 and Ehbp1l1, whose insulin-responsive phosphorylation correlated with insulin-stimulated glucose uptake across individuals; both proteins have known genetic associations with human glycemic traits and could serve as therapeutic targets for conditions such as type 2 diabetes. In a related experiment the researchers measured about 1,000 metabolites and found that about 40% changed with calorie restriction within each sex. The work was funded by the National Institutes of Health and the Australian Research Council, and included coauthors from the University of Michigan, University of Sydney, University of Cambridge, and Royal Children's Hospital. Source: University of Michigan.
Difficult words
- phosphorylation — Chemical change that alters protein activity
- uptake — Absorption or entry into cells or tissues
- calorie restriction — Eating fewer calories than usual
- metabolite — Small molecule produced by biochemical processesmetabolites
- correlate — Change that relates to another measurementcorrelated
- therapeutic — Used to treat disease or medical conditions
- glycemic — Related to blood sugar levels
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Discussion questions
- Why might males and females use different molecular strategies to reach similar improvements in muscle sugar metabolism?
- What are the potential benefits and challenges of targeting Lmod1 and Ehbp1l1 for treating conditions like type 2 diabetes?
- Based on the study, how could calorie restriction influence aging muscle in humans, and what practical concerns would you consider?
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