Voluntary Exercise Promotes Beneficial Anti-aging Mechanisms in SAMP8 Female Brain

Abstract

Regular physical exercise mediates health and longevity promotion involving Sirtuin 1 (SIRT1)-regulated pathways. The anti-aging activity of SIRT1 is achieved, at least in part, by means of fine-tuning the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway by preventing the transition of an originally pro-survival program into a pro-aging mechanism. Additionally, SIRT1 promotes mitochondrial function and reduces the production of reactive oxygen species (ROS) through regulating peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), the master controller of mitochondrial biogenesis. Here, by using senescence-accelerated mice prone 8 (SAMP8) as a model for aging, we determined the effect of wheel-running as a paradigm for long-term voluntary exercise on SIRT1-AMPK pathway and mitochondrial functionality measured by oxidative phosphorylation (OXPHOS) complex content in the hippocampus and cortex. We found differential activation of SIRT1 in both tissues and hippocampal-specific activation of AMPK. These findings correlated well with significant changes in OXPHOS in the hippocampal, but not in the cerebral cortex, area. Collectively, the results revealed greater benefits of the exercise in the wheel-running intervention in a murine model of senescence, which was directly related with mitochondrial function and which was mediated through the modulation of SIRT1 and AMPK pathways.

SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions

“…By the end of 2016, SAMP8 studies appearing in PubMed searches yielded approximately 600 studies. These include the following areas: Alzheimer disease 174; memory deficits 170; dementia 112; Binswanger's disease/vascular dementia 5; Parkinson's disease 5; hydrocephalus 1; oxidative stress 134; amyloid 121; tau 46; neurodegeneration 42; glia 24; therapies 171 (including memory deficits 70 and Alzheimer disease 76); diet 49; neuroprotective effect 26; acupuncture 12; physical exercise 16; and brain insulin 11 …”

Exercise-mimetic AICAR transiently benefits brain function

“…Consistently, thirty days of running elevates hippocampal PGC-1α levels, and eight weeks of treadmill training elevates PGC-1α and Sirtuin 1, increasing brain mitochondrial biogenesis [ 70 ]. In addition, eight weeks of voluntary exercise increased phosphorylation of AMPK in the hippocampus of senescence-accelerated mice [ 71 ]. These changes may mediate synaptic plasticity and spine formation [ 70 , 72 ].…”

Radical Oxygen Species, Exercise and Aging: An Update

“…The antiaging activity of SIRT1 is achieved, at least in part, by means of fine-tuning of the AMPK pathway through prevention of the transition of an originally pro-survival programme into a pro-aging mechanism. Additionally, SIRT1 promotes mitochondrial function and reduces the production of ROS through regulation of peroxisome proliferatoractivated receptor c coactivator (PGC)-1a, the master controller of mitochondrial biogenesis [101]. Figure 3 presents the relationship between training intensity and oxidative stress adaptation in older adults.…”