TY - JOUR
T1 - Initiation of calorie restriction in middle-aged male rats attenuates aging-related motoric decline and bradykinesia without increased striatal dopamine
AU - Salvatore, Michael F.
AU - Terrebonne, Jennifer
AU - Fields, Victoria
AU - Nodurft, Danielle
AU - Runfalo, Cori
AU - Latimer, Brian
AU - Ingram, Donald K.
N1 - Funding Information:
This work was funded by National Institute on Aging grant R01AG040261 . The funding source had no involvement in the study design, data collection, analysis, or interpretation.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Aging-related bradykinesia affects ∼15% of those reaching age 65 and 50% of those reaching their 80s. Given this high risk and lack of pharmacologic therapeutics, noninvasive 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 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 that 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 dopamine neurotransmission may be one component of preserving locomotor capabilities during aging.
AB - Aging-related bradykinesia affects ∼15% of those reaching age 65 and 50% of those reaching their 80s. Given this high risk and lack of pharmacologic therapeutics, noninvasive 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 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 that 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 dopamine neurotransmission may be one component of preserving locomotor capabilities during aging.
KW - Bradykinesia
KW - Caloric restriction
KW - Dopamine
KW - Parkinsonism
KW - Striatum
KW - Substantia nigra
UR - http://www.scopus.com/inward/record.url?scp=84947609610&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2015.10.006
DO - 10.1016/j.neurobiolaging.2015.10.006
M3 - Article
C2 - 26610387
AN - SCOPUS:84947609610
SN - 0197-4580
VL - 37
SP - 192
EP - 207
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -