No decline in skeletal muscle oxidative capacity with aging in long-term calorically restricted rats: Effects are independent of mitochondrial DNA integrity

No decline in skeletal muscle oxidative capacity with aging in long-term calorically restricted rats: Effects are independent of mitochondrial DNA integrity
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DOI:
10.1093/gerona/61.7.675
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发表时间:
2006-07-01
影响因子:
5.1
通讯作者:
Hepple, Russell T.
Hepple, Russell T.
中科院分区:
医学1区
文献类型:
--
作者:
Baker, David J.;Betik, Andrew C.;Hepple, Russell T.

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我们调查了热量限制(CR)在通过CR延长寿命后是否随着年龄的增长而保持骨骼肌的氧化能力,并确定了线粒体含量,线粒体DNA完整性和过氧化物酶体增殖物激活受体γ共激活因子-1 α(PGC-1 α)是否参与其中。研究了自由采食(AL)和CR动物(代表青年、中年晚期和衰老)。而柠檬酸合酶和复合物IV活性较低的跖肌和腓肠肌的年轻成年CR动物,在衰老的AL动物的15%-40%的下降相反,有没有下降,随着年龄的CR动物。两组腓肠肌中柠檬酸合酶蛋白没有随着年龄的增长而下降,这表明CR通过保护线粒体功能而不是内容来保护氧化能力。这种保护作用与组间线粒体DNA损伤无关。然而,与AL动物相比,CR动物中PGC-1 α基因表达随衰老下降较慢,表明CR动物中线粒体生物合成随衰老更好地维持。
We investigated if calorie restriction (CR) preserved skeletal muscle oxidative capacity with aging after accounting for life span extension by CR, and determined if mitochondrial content, mitochondrial DNA integrity, and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) were involved. Ad libitum-fed (AL) and CR animals representing young adult, late middle age, and senescence were studied. Whereas citrate synthase and complex IV activities were lower in plantaris and gastrocnemius muscle of young adult CR animals, in contrast to the 15%-40% decline in senescent AL animals, there was no decline with aging in CR animals. There was no decline in citrate synthase protein in gastrocnemius with aging in either group, suggesting that CR preserves oxidative capacity with aging by protecting mitochondrial function rather than content. This protection was independent of mitochondrial DNA damage between groups. However, there was a slower decline in PGC-1 alpha gene expression with aging in CR versus AL animals, suggesting a better maintenance of mitochondrial biogenesis with aging in CR animals.