Salvatore Michael F, Terrebonne Jennifer, Cantu Mark A, McInnis Tamara R, Venable Katy, Kelley Parker, Kasanga Ella A, Latimer Brian, Owens Catherine L, Pruett Brandon S, Yu Yongmei, Luedtke Robert, Forster Michael J, Sumien Nathalie, Ingram Donald K
Institute for Healthy Aging and Center for Neuroscience Discovery, University of North Texas Health Science Center, Fort Worth.
Pennington Biomedical Research Center, Baton Rouge, Louisiana.
J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):11-20. doi: 10.1093/gerona/glx119.
The escalating increase in retirees living beyond their eighth decade brings increased prevalence of aging-related impairments, including locomotor impairment (Parkinsonism) that may affect ~50% of those reaching age 80, but has no confirmed neurobiological mechanism. Lifestyle strategies that attenuate motor decline, and its allied mechanisms, must be identified. Aging studies report little to moderate loss of striatal dopamine (DA) or tyrosine hydroxylase (TH) in nigrostriatal terminals, in contrast to ~70%-80% loss associated with bradykinesia onset in Parkinson's disease. These studies evaluated the effect of ~6 months 30% calorie restriction (CR) on nigrostriatal DA regulation and aging-related locomotor decline initiated at 12 months of age in Brown-Norway Fischer F1 hybrid rats. The aging-related decline in locomotor activity was prevented by CR. However, striatal DA or TH expression was decreased in the CR group, but increased in substantia nigra versus the ad libitum group or 12-month-old cohort. In a 4- to 6-month-old cohort, pharmacological TH inhibition reduced striatal DA ~30%, comparable with decreases reported in aged rats and the CR group, without affecting locomotor activity. The dissociation of moderate striatal DA reduction from locomotor activity seen in both studies suggests that aging-related decreases in striatal DA are dissociated from locomotor decline.
八十岁以上退休人员数量的不断增加，使得与衰老相关的机能障碍患病率上升，其中包括运动机能障碍（帕金森症），约50%的80岁老人可能受其影响，但目前尚无确凿的神经生物学机制。必须确定能够减缓运动功能衰退及其相关机制的生活方式策略。衰老研究报告显示，黑质纹状体终末的纹状体多巴胺（DA）或酪氨酸羟化酶（TH）仅有轻度至中度损失，而帕金森病中与运动迟缓发作相关的损失约为70%-80%。这些研究评估了在12月龄的布朗-挪威Fischer F1杂交大鼠中，约6个月30%热量限制（CR）对黑质纹状体DA调节及与衰老相关的运动功能衰退的影响。CR预防了与衰老相关的运动活动衰退。然而，CR组纹状体DA或TH表达降低，但与自由进食组或12月龄大鼠队列相比，黑质中的表达增加。在4至6月龄的大鼠队列中，药理学上抑制TH可使纹状体DA降低约30%，与老年大鼠和CR组报告的降低程度相当，且不影响运动活动。两项研究中均观察到纹状体DA适度降低与运动活动之间的分离，这表明与衰老相关的纹状体DA降低与运动功能衰退无关。
