RAD140 (Testolone) negatively impacts skeletal muscle adaptation, frailty status and mortality risk in female mice

Clin Exp Pharmacol Physiol. 2023 Dec;50(12):973-983. doi: 10.1111/1440-1681.13824. Epub 2023 Sep 27.

Abstract

RAD140 is a selective androgen receptor modulator that produces anabolic effects within skeletal muscle. Thus, RAD140 may be effective at treating sarcopenia. No long-term studies have investigated how RAD140 influences strength in ageing muscle. This study aimed to determine how 10 weeks of RAD140 supplementation impacts strength, recovery from exercise, and overall health in ageing mice. Young and adult females were assigned to receive RAD140 (5 mg/kg) or a control solution. Dorsiflexor muscles were exposed to repeated bouts of eccentric contractions, and torque was measured before and after each bout. Adaptive potential and strength gains were calculated to assess the efficacy of RAD140 in muscle, while frailty status and mortality risk were used to measure health span. Supplementation of RAD140 increased frailty status and mortality risk in the young and adult treated groups compared to the controls (p ≤ 0.042). RAD140 decreased adaptive potential in young (p = 0.040) but not adult mice (p = 0.688). Torque did not differ between groups after 2-3 weeks of recovery (p ≥ 0.135). In conclusion, long-term RAD140 supplementation reduced indices of overall health and failed to improve strength in female mice, suggesting that RAD140 (at a 5mg/kg dosage) may be more detrimental than beneficial in delaying or preventing sarcopenia.

Keywords: SARM; androgen; eccentric contraction; resistance training; sarcopenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Frailty*
  • Mice
  • Muscle Contraction / physiology
  • Muscle Strength / physiology
  • Muscle, Skeletal / physiology
  • Nitriles
  • Sarcopenia* / prevention & control

Substances

  • RAD140
  • Nitriles