Chronic caloric restriction preserves mitochondrial function in senescence without increasing mitochondrial biogenesis.
Chronic caloric restriction preserves mitochondrial function in senescence without increasing mitochondrial biogenesis.
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DOI：
10.1016/j.cmet.2012.11.003
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发表时间：
2012-12-05
期刊：
影响因子：
29
通讯作者：
Nair KS
中科院分区：
文献类型：
--
作者：
Lanza IR;Zabielski P;Klaus KA;Morse DM;Heppelmann CJ;Bergen HR 3rd;Dasari S;Walrand S;Short KR;Johnson ML;Robinson MM;Schimke JM;Jakaitis DR;Asmann YW;Sun Z;Nair KS
热量限制（CR）减轻了衰老和延长寿命的许多不利影响。CR已被建议增加线粒体生物合成，从而减弱与年龄相关的线粒体功能下降;这一概念受到最近研究的挑战。在这里，我们表明，终身CR在小鼠中防止与年龄相关的线粒体氧化能力和效率的损失，在分离的线粒体和透化肌纤维测量。我们发现CR的这些有益作用在不增加线粒体丰度的情况下发生。全基因组表达谱分析和大规模蛋白质组学调查显示，表达模式与线粒体生物合成增加不一致，这进一步得到了CR较低的线粒体蛋白质合成的支持。我们发现，CR减少氧化剂排放，增加抗氧化剂清除，并最大限度地减少对DNA和蛋白质的氧化损伤。这些结果表明，CR通过保护现有细胞组分的完整性和功能而不是通过增加线粒体生物合成来保留线粒体功能。
Caloric restriction (CR) mitigates many detrimental effects of aging and prolongs lifespan. CR has been suggested to increase mitochondrial biogenesis, thereby attenuating age-related declines in mitochondrial function; a concept that is challenged by recent studies. Here we show that lifelong CR in mice prevents age-related loss of mitochondrial oxidative capacity and efficiency, measured in isolated mitochondria and permeabilized muscle fibers. We find that these beneficial effects of CR occur without increasing mitochondrial abundance. Whole-genome expression profiling and large-scale proteomic surveys revealed expression patterns inconsistent with increased mitochondrial biogenesis, which is further supported by lower mitochondrial protein synthesis with CR. We find that CR decreases oxidant emission, increases antioxidant scavenging, and minimizes oxidative damage to DNA and protein. These results demonstrate that CR preserves mitochondrial function by protecting the integrity and function of existing cellular components rather than by increasing mitochondrial biogenesis.
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影响因子：
15.8
作者：
Civitarese AE;Carling S;Heilbronn LK;Hulver MH;Ukropcova B;Deutsch WA;Smith SR;Ravussin E;CALERIE Pennington Team
通讯作者：
CALERIE Pennington Team
影响因子：
4.8
作者：
Hancock, Chad R.;Han, Dong-Ho;Holloszy, John O.
通讯作者：
Holloszy, John O.
DOI：
10.1056/nejm197003052821026
发表时间：
1970-03-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cahill, G F Jr
通讯作者：
Cahill, G F Jr
影响因子：
4.8
作者：
Henderson, Gregory C.;Dhatariya, Ketan;Nair, K. Sreekumaran
通讯作者：
Nair, K. Sreekumaran
影响因子：
15.9
作者：
Anderson, Ethan J.;Lustig, Mary E.;Neufer, P. Darrell
通讯作者：
Neufer, P. Darrell