Initiation of calorie restriction in middle-aged male rats attenuates aging-related motoric decline and bradykinesia without increased striatal dopamine

Abstract

Aging-related bradykinesia affects ~15% of those reaching age 65 and 50% of those reaching their 80s. Given this high risk and lack of pharmacological therapeutics, non-invasive lifestyle strategies should be identified to diminish its risk and identify the neurobiological targets to reduce aging-related bradykinesia. Early-life, long-term calorie restriction (CR) attenuates aging-related bradykinesia in rodents. Here, we addressed whether CR initiation at middle age could attenuate aging-related bradykinesia and motoric decline measured as rotarod performance. A 30% CR regimen was implemented for 6 months duration in 12-month old male Brown-Norway Fischer 344 F1 hybrid rats after establishing individual baseline locomotor activities. Locomotor capacity was assessed every 6 weeks thereafter. The ad libitum (AL) group exhibited predictably decreased locomotor activity, except movement speed, out to 18 months of age. In contrast, in the CR group, movement number and horizontal activity did not decrease during the 6-month trial and aging-related decline in rotarod performance was attenuated. The response to CR was influenced by baseline locomotor activity. The lower the locomotor activity level at baseline, the greater the response to CR. Rats in the lower 50th percentile surpassed their baseline level of activity, whereas rats in the top 50th percentile decreased at 6 weeks and then returned to baseline by 12 weeks of CR. We hypothesized that nigrostriatal dopamine tissue content would be greater in the CR group and observed a modest increase only in substantia nigra with no group differences in striatum, nucleus accumbens, or ventral tegmental area. These results indicate initiation of CR at middle age may reduce aging-related bradykinesia and, furthermore, subjects with below average locomotor activity may increase baseline activity. Sustaining nigral DA neurotransmission may be one component of preserving locomotor capabilities during aging.

Caloric restriction and redox homeostasis in various regions of aging male rat brain: Is caloric restriction still worth trying even after early-adulthood?

“…Therefore, the protective effects of CR on redox homeostasis in aging brain seem to be preserved when CR is inducted around the middle adulthood. These findings are very consistent with the previous research in the same age group of mice, where functional loss was documented (Salvatore et al, ).…”

“…These findings are very consistent with the previous research in the same age group of mice, where functional loss was documented (Salvatore et al, 2016(Salvatore et al, , 2017.…”

“…The purpose of the current study was to link the recently documented neurodegenerative alterations in aging rats and metabolic alterations that are likely to play a role in the etiology of these deficits by investigating the metabolomic effects of CR (when the neurodegenerative processes are already underway) on the redox status of different anatomical parts of the aging rat brain (Salvatore et al, ). Therefore, our study focused on CR and how nutritional interventions could modulate redox status during aging process in various rat brain regions.…”

“…Thus, understanding of biochemical alterations remains at a preliminary stage. Despite CR seems to be an effective strategy in slowing down the rate of brain aging, a comprehensive metabolomic understanding of brain aging linking the previously observed increased life span and improved functional activity when neural decline has already started is lacking (Pifferi et al, ; Salvatore et al, ; Van Cauwenberghe et al, ; Yang et al, ). Cellular formation and the elimination of oxidatively damaged products represent considerable variations during biological aging process and age‐related neurovascular diseases.…”

Calorie restriction in rodents: Caveats to consider

“…Singh et al introduced an IF regimen (EOD) to 21-mo old male Wistar rats for 3 months and noted significant improvements in motor performance (rotarod test) and cognition (MWM) (Singh et al, 2012). Salvatore et al reported that 30% CR introduced to F344BNF1 rats at 12 mo of age significantly attenuated the longitudinal decline in locomotor behavior measured in the open field (Salvatore et al, 2016). …”