TY - JOUR
T1 - Losartan improves measures of activity, inflammation, and oxidative stress in older mice
AU - Lin, Chung Hao
AU - Yang, Huanle
AU - Xue, Qian Li
AU - Chuang, Yi Fang
AU - Roy, Cindy N.
AU - Abadir, Peter
AU - Walston, Jeremy D.
N1 - Funding Information:
This work is supported by the Johns Hopkins University Claude D. Pepper Older Americans Independence Center, National Institute on Aging (NIA) , P30AG021334 . The authors gratefully thank Jackie Langdon for performing the mouse husbandry in support of this project, and Denise Baldwin for manuscript preparation.
PY - 2014/10
Y1 - 2014/10
N2 - 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. ±. 59.5. pg/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.
AB - 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. ±. 59.5. pg/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.
KW - Angiotensin II receptor blocker
KW - Frailty
KW - Inflammation
KW - Oxidative stress
KW - Renin-angiotensin system
KW - Sarcopenia
UR - http://www.scopus.com/inward/record.url?scp=84907353142&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2014.07.017
DO - 10.1016/j.exger.2014.07.017
M3 - Article
C2 - 25077714
AN - SCOPUS:84907353142
SN - 0531-5565
VL - 58
SP - 174
EP - 178
JO - Experimental Gerontology
JF - Experimental Gerontology
ER -