Antioxidant enzymes and Nrf2/Keap1 in human skeletal muscle: Influence of age, sex, adiposity and aerobic fitness

Victor Galvan-Alvarez; Angel Gallego-Selles; Miriam Martinez-Canton; Eduardo García-Gonzalez; Miriam Gelabert-Rebato; Jesus Gustavo Ponce-Gonzalez; Steen Larsen; David Morales-Alamo; Jose Losa-Reyna; Ismael Perez-Suarez; Cecilia Dorado; Mario Perez-Valera; Hans-Christer Holmberg; Robert Boushel; Pedro de Pablos Velasco; Jorn Wulff Helge; Marcos Martin-Rincon; Jose A L Calbet

doi:10.1016/j.freeradbiomed.2023.10.393

Antioxidant enzymes and Nrf2/Keap1 in human skeletal muscle: Influence of age, sex, adiposity and aerobic fitness

Free Radic Biol Med. 2023 Nov 20;209(Pt 2):282-291. doi: 10.1016/j.freeradbiomed.2023.10.393. Epub 2023 Oct 17.

Authors

Victor Galvan-Alvarez¹, Angel Gallego-Selles¹, Miriam Martinez-Canton¹, Eduardo García-Gonzalez¹, Miriam Gelabert-Rebato¹, Jesus Gustavo Ponce-Gonzalez², Steen Larsen³, David Morales-Alamo¹, Jose Losa-Reyna², Ismael Perez-Suarez¹, Cecilia Dorado¹, Mario Perez-Valera¹, Hans-Christer Holmberg⁴, Robert Boushel⁵, Pedro de Pablos Velasco⁶, Jorn Wulff Helge⁷, Marcos Martin-Rincon¹, Jose A L Calbet⁸

Affiliations

¹ Department of Physical Education, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, Las Palmas de Gran Canaria, 35017, Spain; Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Paseo Blas Cabrera Felipe "Físico" s/n, 35017, Las Palmas de Gran Canaria, Spain.
² Department of Physical Education, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, Las Palmas de Gran Canaria, 35017, Spain.
³ Center of Healthy Ageing, Department of Biomedical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark; Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
⁴ Department of Health Sciences, Luleå University of Technology, Sweden; School of Kinesiology, Faculty of Education, The University of British Columbia, Vancouver, BC, Canada.
⁵ School of Kinesiology, Faculty of Education, The University of British Columbia, Vancouver, BC, Canada.
⁶ Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Paseo Blas Cabrera Felipe "Físico" s/n, 35017, Las Palmas de Gran Canaria, Spain; Department of Endocrinology and Nutrition, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain.
⁷ Center of Healthy Ageing, Department of Biomedical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
⁸ Department of Physical Education, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, Las Palmas de Gran Canaria, 35017, Spain; Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Paseo Blas Cabrera Felipe "Físico" s/n, 35017, Las Palmas de Gran Canaria, Spain; School of Kinesiology, Faculty of Education, The University of British Columbia, Vancouver, BC, Canada; Department of Physical Performance, The Norwegian School of Sport Sciences, Postboks, 4014 Ulleval Stadion, 0806, Oslo, Norway. Electronic address: lopezcalbet@gmail.com.

PMID: 37858747
DOI: 10.1016/j.freeradbiomed.2023.10.393

Abstract

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^{^-1}can 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.

Keywords: Aging; Catalase; Free radicals; Nrf2; Obesity; Physical activity; ROS; SOD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adiposity*
Antioxidants*
Catalase / genetics
Female
Glutathione Reductase
Humans
Kelch-Like ECH-Associated Protein 1 / genetics
Male
Muscle, Skeletal
NF-E2-Related Factor 2 / genetics
Obesity / genetics
Superoxide Dismutase-1

Substances

Antioxidants
Catalase
NF-E2-Related Factor 2
Superoxide Dismutase-1
Kelch-Like ECH-Associated Protein 1
Glutathione Reductase