MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.
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DOI：
10.1038/s41467-020-20790-0
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发表时间：
2021-01-20
影响因子：
16.6
通讯作者：
Lee C
中科院分区：
文献类型：
--
作者：
Reynolds JC;Lai RW;Woodhead JST;Joly JH;Mitchell CJ;Cameron-Smith D;Lu R;Cohen P;Graham NA;Benayoun BA;Merry TL;Lee C
健康的老龄化可以通过增强新陈代谢和体能来促进。线粒体是主要的代谢细胞器，在衰老中具有强烈的意义，其也部分地使用在其独立基因组内编码的肽来协调广泛的生理功能。然而，积极调节衰老的大脑编码因子是未知的。在这里，我们报告说，大脑编码的MOTS-c可以显着提高年轻人（2个月）的身体表现，中年（12个月），老（22个月）小鼠MOTS-c可以调节（i）核基因，包括与代谢和蛋白质稳态相关的那些，（ii）骨骼肌代谢，和（iii）成肌细胞对代谢应激的适应。我们提供的证据表明，晚年（23.5个月）起始的间歇性MOTS-c治疗（3x/周）可以增加小鼠的体能和健康寿命。在人类中，运动诱导骨骼肌和循环中的内源性MOTS-c表达。我们的数据表明，衰老是由我们共同进化的线粒体和核基因组中编码的基因调控的。运动对老年生物体的新陈代谢和整体生理健康有有益的影响。在这里，作者表明MOTS-c是一种由唾液酸编码的运动诱导肽，可以调节骨骼肌代谢，改善老年小鼠的健康寿命。
Healthy aging can be promoted by enhanced metabolic fitness and physical capacity. Mitochondria are chief metabolic organelles with strong implications in aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome. However, mitochondrial-encoded factors that actively regulate aging are unknown. Here, we report that mitochondrial-encoded MOTS-c can significantly enhance physical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice. MOTS-c can regulate (i) nuclear genes, including those related to metabolism and proteostasis, (ii) skeletal muscle metabolism, and (iii) myoblast adaptation to metabolic stress. We provide evidence that late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) can increase physical capacity and healthspan in mice. In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation. Our data indicate that aging is regulated by genes encoded in both of our co-evolved mitochondrial and nuclear genomes. Exercise has beneficial effects on metabolism and overall physiologic fitness in aged organisms. Here the authors show that MOTS-c is a mitochondrial-encoded exercise-induced peptide that regulates skeletal muscle metabolism and improves healthspan of older mice.
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影响因子：
64.5
作者：
Gottschling DE;Nyström T
通讯作者：
Nyström T
影响因子：
29
作者：
Goodpaster BH;Sparks LM
通讯作者：
Sparks LM
影响因子：
29
作者：
Brandhorst S;Choi IY;Wei M;Cheng CW;Sedrakyan S;Navarrete G;Dubeau L;Yap LP;Park R;Vinciguerra M;Di Biase S;Mirzaei H;Mirisola MG;Childress P;Ji L;Groshen S;Penna F;Odetti P;Perin L;Conti PS;Ikeno Y;Kennedy BK;Cohen P;Morgan TE;Dorff TB;Longo VD
通讯作者：
Longo VD
影响因子：
16.6
作者：
Kauffman WB;Guha S;Wimley WC
通讯作者：
Wimley WC
影响因子：
7.8
作者：
Fuku N;Pareja-Galeano H;Zempo H;Alis R;Arai Y;Lucia A;Hirose N
通讯作者：
Hirose N