caloric restriction shortens lifespan through an increase in lipid peroxidation, inflammation and apoptosis in the g93a mouse, an animal model of als热量限制缩短寿命通过脂质过氧化增加,炎症和细胞凋亡在g93a鼠标,als的动物模型.pdfVIP

Caloric Restriction Shortens Lifespan through an Increase in Lipid Peroxidation, Inflammation and Apoptosis in the G93A Mouse, an Animal Model of ALS 1,2 3,4,5 3 3,4 1,2,3 Barkha P. Patel , Adeel Safdar , Sandeep Raha , Mark A. Tarnopolsky , Mazen J. Hamadeh * 1 School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada, 2 Muscle Health Research Centre, York University, Toronto, Ontario, Canada, 3 Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada, 4 Department of Medicine, McMaster University, Hamilton, Ontario, Canada, 5 Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada Abstract Caloric restriction (CR) extends lifespan through a reduction in oxidative stress, delays the onset of morbidity and prolongs lifespan. We previously reported that long-term CR hastened clinical onset, disease progression and shortened lifespan, while transiently improving motor performance in G93A mice, a model of amyotrophic lateral sclerosis (ALS) that shows increased free radical production. To investigate the long-term CR-induced pathology in G93A mice, we assessed the mitochondrial bioenergetic efficiency and oxidative capacity (CS – citrate synthase content and activity, cytochrome c oxidase - COX activity and protein content of COX subunit- I and IV and UCP3- uncoupling protein 3), oxidative damage (MDA – malondialdehyde and PC – protein carbonyls), antioxidant enzyme capacity (Mn-SOD, Cu/Zn-SOD and catalase), inflammation (TNF-a), stress response (Hsp70) and markers of apoptosis (Bax, Bcl-2, caspase 9, cleaved caspase 9) in their skeletal muscle. At age 40 days, G93A