Caloric restriction attenuates motor function decline in rats: Evidence from an advanced middle-aged cohort

Purpose: The maintenance of physical function is a hallmark of successful aging. This is, however, not achievable for every individual. In the rapidly aging elderly population, between 30-50% may suffer from locomotor impairment as a function of aging, a phenomenon known as aging-related parkinsonism. This motor impairment is a serious public health concern as it greatly compromises the ability to perform daily life activities, further contributing to loss of independent living, frailty, and mortality. In this population, lifestyle strategies could prove beneficial for reducing aging-related parkinsonism. Caloric restriction (CR) can reduce aging-related locomotor decline when instituted either as a lifelong intervention or during middle age in rats. This study seeks to determine if there is an aging-related limit of caloric restriction efficacy to attenuate motor decline and if nigrostriatal dopamine regulation is associated with motor effects. Method: Male Brown-Norway/Fischer 344 F1 hybrid (BNF) rats (18 months old) previously maintained on a lifelong ad libitum (AL) diet were grouped into CR and AL groups. CR was gradually introduced with a 30% restriction being achieved 3 weeks after initiation of the study. This was maintained for 6 months with open-field locomotor assessments conducted every 6 weeks. Results: CR prevented decreased motor function as a function of aging; an effect that was observed in the AL group. There was an increase in movement number and horizontal activity which are both indices of the ability to initiate movement. Significant decline in motor function was observed in the AL group 12 weeks after initiation of the study and this effect was sustained till the end of the study. Conclusion: Caloric restriction initiated in advanced middle-aged rats leads to a preservation of motor function suggesting that there may be no aging limit to its beneficial effect on motor performance. Identifying the molecular mechanisms can reveal targets for pharmacological or genetic approaches to mitigate motor impairment in individuals where CR would be contraindicated.