title: Losartan improves measures of activity, inflammation, and oxidative stress in older mice.
abstract: Sarcopenia is an age-related decline in skeletal muscle mass and function that is multifactorial in etiology. Age-related changes in the renin-angiotensin system (RAS), increased oxidative stress, and chronic inflammation likely all contribute to its development. Losartan, an angiotensin II type I receptor blocker (ARB) decreases RAS activity and likely influences oxidative stress and inflammation. Given this, we hypothesized that losartan would improve activity levels and parameters related to inflammation and oxidative stress in older mice. We sought to test this hypothesis by comparing functional and molecular parameters between 18-month-old C57BL/6 mice treated with 50-70 mg/kg/day of losartan over a 4 month-period and age- and gender-matched mice receiving placebo. Losartan treatment significantly improved several activity measurements during treatment period compared to placebo controlled group, including increased time on treadmill, traveling activity, standing activity, and decreased grid contacts (p-values<0.05, 0.001, 0.01; and 0.04 respectively). Grip strength did not improve in treatment group relative to control group over time. Serum IL-6 level in the treated group was significantly lower than that in the control group at the end of treatment (30.3±12.9 vs. 173.0±59.5pg/ml, p<0.04), and mRNA expression of antioxidant enzymes catalase (3.9±0.9 vs. 1.0±0.4) and glutathione peroxidase (4.7±1.1 vs. 1.0±0.4) was significantly higher (p-value: 0.02, and 0.03 respectively) in quadriceps muscle after 4 months of treatment in treated and control groups. These results support the hypothesis that chronic losartan treatment improves skeletal muscle related activity measures in older mice, and that it is associated with more favorable relevant biological profiles in the treatment group. Additional studies are needed to 1) further quantify this functional improvement, 2) further identify mechanisms that influence this improvement, and 3) provide additional rationale for translating these findings into older adults.
authors: Department of Medicine, Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD, USA; Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Chung-Hao
authors: CH
authors: Lin
authors: Department of Medicine, Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD, USA.
authors: Huanle
authors: H
authors: Yang
authors: Department of Medicine, Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD, USA.
authors: Qian-Li
authors: QL
authors: Xue
authors: Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors: Yi-Fang
authors: YF
authors: Chuang
authors: Department of Medicine, Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD, USA.
authors: Cindy N
authors: CN
authors: Roy
authors: Department of Medicine, Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD, USA.
authors: Peter
authors: P
authors: Abadir
authors: Department of Medicine, Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, MD, USA. Electronic address: jwalston@jhmi.edu.
authors: Jeremy D
authors: JD
authors: Walston
mesh_terms: D000367:Age Factors; D000375:Aging; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D019808:Losartan / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D055948:Sarcopenia / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D018836:Inflammation Mediators; D015850:Interleukin-6; C577686:interleukin-6, mouse; D002374:Catalase; D005979:Glutathione Peroxidase; D019808:Losartan
keywords: Angiotensin II receptor blocker; Frailty; Inflammation; Oxidative stress; Renin–angiotensin system; Sarcopenia