Voluntary aerobic exercise increases arterial resilience and mitochondrial health with aging in mice

Abstract

Mitochondrial dysregulation and associated excessive reactive oxygen species (mtROS) production is a key source of oxidative stress in aging arteries that reduces baseline function and may influence resilience (ability to withstand stress). We hypothesized that voluntary aerobic exercise would increase arterial resilience in old mice. An acute mitochondrial stressor (rotenone) caused greater (further) impairment in peak carotid EDD in old (~27 mo., OC, n=12;−32.5±-10.5%) versus young (~7 mo., YC n=11;−5.4±- 3.7%) control male mice, whereas arteries from young and old exercising (YVR n=10 and OVR n=11, 10-wk voluntary running;−0.8±-2.1% and −8.0±4.9%, respectively) mice were protected. Ex-vivo simulated Western diet (WD, high glucose and palmitate) caused greater impairment in EDD in OC (-28.5±8.6%) versus YC (-16.9±5.2%) and YVR (-15.3±2.3%), whereas OVR (-8.9±3.9%) were more resilient (not different versus YC). Simultaneous ex-vivo treatment with mitochondria-specific antioxidant MitoQ attenuated WD-induced impairments in YC and OC, but not YVR or OVR, suggesting that exercise improved resilience to mtROS-mediated stress. Exercise normalized age-related alterations in aortic mitochondrial protein markers PGC-1α, SIRT-3 and Fis1 and augmented cellular antioxidant and stress response proteins. Our results indicate that arterial aging is accompanied by reduced resilience and mitochondrial health, which are restored by voluntary aerobic exercise.

Mitochondrial Function and Mitophagy in the Elderly: Effects of Exercise

“…Some studies that relate autophagy and/or mitochondrial function to the aging process show results that may be different [ 10 , 42 – 44 ]. Specifically, regarding proteins involved in biogenesis, most studies found a decrease in mRNA and protein expression of PGC-1 α [ 45 – 53 ]. These data indicate that, during aging, the reduced mitochondrial biogenesis may be due to the lack of response of PGC-1 α to different stimuli.…”

“…In this line, Mfn1 and Mfn2 also increased in mouse and rat muscles during senescence [ 43 , 44 , 48 , 59 – 61 ]. However, other studies point to an absence of changes or even decreases in these proteins responsible for mitochondrial fusion [ 30 , 45 , 46 , 58 , 60 , 64 – 66 ]. On the other hand, and as previously mentioned, mitophagy is promoted by fission [ 18 ].…”

“…These results reinforce the possibility that OPA1 might act as an inhibitor of mitochondrial fission [ 64 ]. However, results about the role of Fis1 protein in the aging process are not conclusive [ 30 , 44 , 45 , 48 , 58 , 59 , 65 – 67 ].…”

Effect of Exercise Training and Middle-Age on Pathological and Physiological Cardiac Hypertrophy

“…Although the role of exercise training through other mechanisms has been less considered, including changes in anti-aging hormones and oxidative stress, MAPKs may be involved in the hypertrophy of the middle-aged heart. In this context, it has also been reported that exercise training can be effective in improving age-related mitochondrial disorders (82,83).…”

Reduced SIRT3 contributes to large elastic artery stiffness with aging

“…Recently, mitochondrial reactive oxygen species (mtROS) have been implicated as a possible cause of the age-associated changes in arterial function and structure (Gioscia-Ryan, Battson, Cuevas, Zigler, & Sindler, 2016) (Dai, Rabinovitch, & Ungvari, 2012). As organisms age, the mitochondrial production of ROS increases in the vasculature because of a decline in overall mitochondrial function, declining activity of ROS scavenging enzymes, and mutations to mitochondrial DNA (Bratic & Larsson, 2013).…”