What Is Sauce for the Gander Is Not Sauce for the Goose: Sexual Dimorphism of Skeletal Muscle Stem Cells in Age and Exercise

Gabi Shefer 1,2,3 Yonit Marcus 1,2 Eli Carmeli 4 Naftali Stern 1,2 Dafna Benayahu 2 Eli Carmeli Naftali Stern Zipora Yablonka-Reuveni 3
1Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Souraski Medical Center, Israel
2Sackler School of Medicine, Tel Aviv University, Israel
3Biological Structure, University of Washington School of Medicine, USA
4Physical Therapy, Faculty of Social Welfare and Health Sciences, University of Haifa, Israel

Background: Aging is associated with sarcopenia, a progressive decline in muscle mass and strength. The repair of myofibers, functional units of skeletal-muscles, depends on satellite cells (SCs), or muscle stem cells. Human and rodent studies show an age-associated decline in SC-numbers which may play a role in sarcopenia.

Aim: to investigate gender-related differences in SCs in response to age and endurance exercise.

Methods: Gastrocnemius or extensor-digitorum-longus muscles of rats and mice were assessed for the effect of age, gender and exercise on SCs. Rodents ran on a treadmill for 20 minutes/day/6days/week, for 13-weeks. Ages (months) at the end of exercise were in rats 6.5, 18-20 and in mice 8, 18-20.

Results: Age: There was an age-associated decline in SC-numbers of sedentary males and females and a sharp increase in myofibers lacking SCs. Myostatin-null-mice with large muscle mass were not spared from age-associated SC decline. Gender: (1) Average number of SCs was 2-3-fold higher in males vs. females in both ages; (2) At old age, male myofibers exhibited a 64% decline in SC-numbers compared to a 34% decline in females. Exercise: In male rats, exercise induced a 25% and 100% increase in SC-numbers, compared to 66% and 50% increases in young and old rats. In mice, gender differences were more dramatic with an increase of 66% and 100% in SCs in males at both ages and only 20% and 40% in females. Our studies underscore the need to further explore the role of sex-hormones in attempted preservation of skeletal-muscle in aging.









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