TY - JOUR

T1 - Antioxidant enzymes and Nrf2/Keap1 in human skeletal muscle

T2 - Influence of age, sex, adiposity and aerobic fitness

AU - Galvan-Alvarez, Victor

AU - Gallego-Selles, Angel

AU - Martinez-Canton, Miriam

AU - García-Gonzalez, Eduardo

AU - Gelabert-Rebato, Miriam

AU - Ponce-Gonzalez, Jesus Gustavo

AU - Larsen, Steen

AU - Morales-Alamo, David

AU - Losa-Reyna, Jose

AU - Perez-Suarez, Ismael

AU - Dorado, Cecilia

AU - Perez-Valera, Mario

AU - Holmberg, Hans Christer

AU - Boushel, Robert

AU - de Pablos Velasco, Pedro

AU - Helge, Jorn Wulff

AU - Martin-Rincon, Marcos

AU - Calbet, Jose A.L.

N1 - Publisher Copyright: © 2023 The Authors

PY - 2023

Y1 - 2023

N2 - Ageing, a sedentary lifestyle, and obesity are associated with increased oxidative stress, while regular exercise is associated with an increased antioxidant capacity in trained skeletal muscles. Whether a higher aerobic fitness is associated with increased expression of antioxidant enzymes and their regulatory factors in skeletal muscle remains unknown. Although oestrogens could promote a higher antioxidant capacity in females, it remains unknown whether a sex dimorphism exists in humans regarding the antioxidant capacity of skeletal muscle. Thus, the aim was to determine the protein expression levels of the antioxidant enzymes SOD1, SOD2, catalase and glutathione reductase (GR) and their regulatory factors Nrf2 and Keap1 in 189 volunteers (120 males and 69 females) to establish whether sex differences exist and how age, VO2max and adiposity influence these. For this purpose, vastus lateralis muscle biopsies were obtained in all participants under resting and unstressed conditions. No significant sex differences in Nrf2, Keap1, SOD1, SOD2, catalase and GR protein expression levels were observed after accounting for VO2max, age and adiposity differences. Multiple regression analysis indicates that the VO2max in mL.kg LLM−1.min−1can be predicted from the levels of SOD2, Total Nrf2 and Keap1 (R = 0.58, P < 0.001), with SOD2 being the main predictor explaining 28 % of variance in VO2max, while Nrf2 and Keap1 explained each around 3 % of the variance. SOD1 protein expression increased with ageing in the whole group after accounting for differences in VO2max and body fat percentage. Overweight and obesity were associated with increased pSer40-Nrf2, pSer40-Nrf2/Total Nrf2 ratio and SOD1 protein expression levels after accounting for differences in age and VO2max. Overall, at the population level, higher aerobic fitness is associated with increased basal expression of muscle antioxidant enzymes, which may explain some of the benefits of regular exercise.

AB - Ageing, a sedentary lifestyle, and obesity are associated with increased oxidative stress, while regular exercise is associated with an increased antioxidant capacity in trained skeletal muscles. Whether a higher aerobic fitness is associated with increased expression of antioxidant enzymes and their regulatory factors in skeletal muscle remains unknown. Although oestrogens could promote a higher antioxidant capacity in females, it remains unknown whether a sex dimorphism exists in humans regarding the antioxidant capacity of skeletal muscle. Thus, the aim was to determine the protein expression levels of the antioxidant enzymes SOD1, SOD2, catalase and glutathione reductase (GR) and their regulatory factors Nrf2 and Keap1 in 189 volunteers (120 males and 69 females) to establish whether sex differences exist and how age, VO2max and adiposity influence these. For this purpose, vastus lateralis muscle biopsies were obtained in all participants under resting and unstressed conditions. No significant sex differences in Nrf2, Keap1, SOD1, SOD2, catalase and GR protein expression levels were observed after accounting for VO2max, age and adiposity differences. Multiple regression analysis indicates that the VO2max in mL.kg LLM−1.min−1can be predicted from the levels of SOD2, Total Nrf2 and Keap1 (R = 0.58, P < 0.001), with SOD2 being the main predictor explaining 28 % of variance in VO2max, while Nrf2 and Keap1 explained each around 3 % of the variance. SOD1 protein expression increased with ageing in the whole group after accounting for differences in VO2max and body fat percentage. Overweight and obesity were associated with increased pSer40-Nrf2, pSer40-Nrf2/Total Nrf2 ratio and SOD1 protein expression levels after accounting for differences in age and VO2max. Overall, at the population level, higher aerobic fitness is associated with increased basal expression of muscle antioxidant enzymes, which may explain some of the benefits of regular exercise.

KW - Aging

KW - Catalase

KW - Free radicals

KW - Nrf2

KW - Obesity

KW - Physical activity

KW - ROS

KW - SOD

UR - http://www.scopus.com/inward/record.url?scp=85175336562&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2023.10.393

DO - 10.1016/j.freeradbiomed.2023.10.393

M3 - Journal article

C2 - 37858747

AN - SCOPUS:85175336562

VL - 209

SP - 282

EP - 291

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

SN - 0891-5849

ER -