Abstract
Identifying lifestyle strategies and allied neurobiological mechanisms that reduce aging-related motor impairment is imperative, given the accelerating number of retirees and increased life expectancy. A physically active lifestyle prior to old age can reduce risk of debilitating motor decline. However, if exercise is initiated after motor decline has begun in the lifespan, it is unknown if aging itself may impose a limit on exercise efficacy to decelerate further aging-related motor decline. In Brown-Norway/Fischer 344 F1 hybrid (BNF) rats, locomotor activity begins to decrease in middle age (12–18 months). One mechanism of aging-related motor decline may be decreased expression of GDNF family receptor, GFRα-1, which is decreased in substantia nigra (SN) between 12 and 30 months old. Moderate exercise, beginning at 18 months old, increases nigral GFRα-1 and tyrosine hydroxylase (TH) expression within 2 months. In aged rats, replenishing aging-related loss of GFRα-1 in SN increases TH in SN alone and locomotor activity. A moderate exercise regimen was initiated in sedentary male BNF rats in a longitudinal study to evaluate if exercise could attenuate aging-related motor decline when initiated at two different ages in the latter half of the lifespan (18 or 24 months old). Motor decline was reversed in the 18-, but not 24-month-old, cohort. However, exercise efficacy in the 18-month-old group was reduced as the rats reached 27 months old. GFRα-1 expression was not increased in either cohort. These studies suggest exercise can decelerate motor decline when begun in the latter half of the lifespan, but its efficacy may be limited by age of initiation. Decreased plasticity of GFRα-1 expression following exercise may limit its efficacy to reverse motor decline.
Highlights
Parkinsonian signs are prevalent in the elderly, affecting ~15% of individuals by age 65 and 50% of individuals by age 80 [1,2,3,4,5,6,7]
In the 18-month-old group, body weights significantly decreased in both exercise and nonexercise groups during the exercise regimen (S1C Fig), with the exercise group losing more weight after rounds 3 and 7
The exercise intervention in this study began after locomotor impairment likely has already occurred, 6 months prior to the earliest intervention at 18 months old [31,32]
Summary
Parkinsonian signs are prevalent in the elderly, affecting ~15% of individuals by age 65 and 50% of individuals by age 80 [1,2,3,4,5,6,7]. The metrics of exercise frequency, intensity, and duration are difficult to accurately establish from self-reporting [23] While these metrics can be controlled in preclinical exercise studies, these studies may not accommodate to the reality that supervised exercise in human studies is conducted for ~3 days/week [13,14,21], leaving at least equal days within a time frame where exercise does not occur. A controlled longitudinal exercise regimen that features exercise compliance to a regimen of fixed duration, intensity, and frequency, and accommodates for consistent rest periods, may provide a realistic and translatable outcome on the efficacy of a given exercise regimen on motor impairments related to aging and its underlying neurobiological mechanisms
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