SIRT3 deficiency decreases oxidative metabolism capacity but increases lifespan in male mice under caloric restriction.
SIRT3 deficiency decreases oxidative metabolism capacity but increases lifespan in male mice under caloric restriction.
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作者：
线粒体 NAD+ 依赖性蛋白脱乙酰酶 Sirtuin3 (SIRT3) 被认为可以介导热量限制 (CR) 依赖性代谢调节和寿命延长。在这里，我们研究了 SIRT3 在 CR 介导的长寿、线粒体功能和有氧健身中的作用。我们报告说，SIRT3 对于全身有氧能力是必需的，但对于 CR 依赖的寿命延长来说是可有可无的。在 CR 条件下，与 Sirt3 +/+ 小鼠相比，SIRT3 (Sirt3 −/− ) 缺失的小鼠总体寿命和最大寿命更长。这种意想不到的寿命延长与氧化代谢途径中线粒体蛋白乙酰化的改变、线粒体呼吸减少和有氧运动能力降低有关。此外，Sirt3 -/− CR 小鼠在餐后表现出较低的自发活动和有利于脂肪酸氧化的趋势。这项研究展示了寿命和健康参数（有氧健身和自发活动）的解耦，并为 SIRT3 在 CR 适应、燃料利用和衰老中的功能提供了新的见解。这项研究表明，寿命和健康寿命参数可以分开，并且线粒体蛋白 SIRT3 是燃料利用、体力活动和衰老的调节剂。
Mitochondrial NAD+‐dependent protein deacetylase Sirtuin3 (SIRT3) has been proposed to mediate calorie restriction (CR)‐dependent metabolic regulation and lifespan extension. Here, we investigated the role of SIRT3 in CR‐mediated longevity, mitochondrial function, and aerobic fitness. We report that SIRT3 is required for whole‐body aerobic capacity but is dispensable for CR‐dependent lifespan extension. Under CR, loss of SIRT3 (Sirt3 −/− ) yielded a longer overall and maximum lifespan as compared to Sirt3 +/+ mice. This unexpected lifespan extension was associated with altered mitochondrial protein acetylation in oxidative metabolic pathways, reduced mitochondrial respiration, and reduced aerobic exercise capacity. Also, Sirt3 −/− CR mice exhibit lower spontaneous activity and a trend favoring fatty acid oxidation during the postprandial period. This study shows the uncoupling of lifespan and healthspan parameters (aerobic fitness and spontaneous activity) and provides new insights into SIRT3 function in CR adaptation, fuel utilization, and aging. This study shows that lifespan and healthspan parameters can be uncoupled and that the mitochondrial protein SIRT3 is a modulator of fuel utilization, physical activity, and aging.
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SIRT3在饮食限制期间促进尿素周期和脂肪酸氧化。
影响因子：
16
作者：
Hallows WC;Yu W;Smith BC;Devries MK;Ellinger JJ;Someya S;Shortreed MR;Prolla T;Markley JL;Smith LM;Zhao S;Guan KL;Denu JM
通讯作者：
Denu JM
SIRT3 线粒体脱乙酰酶在细胞生理学、癌症和神经退行性疾病中的功能。
影响因子：
7.8
作者：
Ansari A;Rahman MS;Saha SK;Saikot FK;Deep A;Kim KH
通讯作者：
Kim KH
影响因子：
64.5
作者：
Fontana L;Partridge L
通讯作者：
Partridge L
影响因子：
13.8
作者：
Baeza J;Smallegan MJ;Denu JM
通讯作者：
Denu JM
影响因子：
7.4
作者：
Bao, Jianjun;Scott, Iain;Lu, Zhongping;Pang, Liyan;Dimond, Christopher C.;Gius, David;Sack, Michael N.
通讯作者：
Sack, Michael N.