Calorie restriction delays skeletal muscle aging through AMPK-SIRT1-mitochondria pathway in mice

Rongxi Pu; Chuanchuan Bai; Dongliang Xie; Weiru Wu; Bin Shu; Zhong Yang

doi:10.16016/j.1000-5404.201610056

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Calorie restriction delays skeletal muscle aging through AMPK-SIRT1-mitochondria pathway in mice

更新时间：2026-01-09

- Calorie restriction delays skeletal muscle aging through AMPK-SIRT1-mitochondria pathway in mice
- Journal of Third Military Medical University Vol. 39, Issue 6, Pages: 548-552(2017)
- 作者机构：
  
  1.400038 重庆，第三军医大学西南医院检验系临床血液学教研室
  2.401121 重庆，重庆医科大学附属大学城医院康复中心
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(31571242)
- DOI：10.16016/j.1000-5404.201610056
  CLC： R151.1; R322.74; R339.34
- Received：11 October 2016，
  
  Revised：2016-11-09，
  
  Published：2017-06
- 稿件说明：
移动端阅览
Rongxi Pu, Chuanchuan Bai, Dongliang Xie, et al. Calorie restriction delays skeletal muscle aging through AMPK-SIRT1-mitochondria pathway in mice[J]. Journal of Third Military Medical University, 2017, 39(6): 548-552.
DOI：

Rongxi Pu, Chuanchuan Bai, Dongliang Xie, et al. Calorie restriction delays skeletal muscle aging through AMPK-SIRT1-mitochondria pathway in mice[J]. Journal of Third Military Medical University, 2017, 39(6): 548-552. DOI： 10.16016/j.1000-5404.201610056.

摘要

目的

观察热量限制对老化进程中小鼠骨骼肌线粒体等生物学性状的影响，探讨热量限制生物效应的分子机制。

方法

13月龄C57BL/6雄性小鼠30只，按照简单随机抽样法分为自由进食组和热量限制组，每周按照自由进食组前1周平均摄食量的60%饲养热量限制小鼠。热量限制12周后，测量骨骼肌衰减指数、胫前肌等肌纤维密度及相对横截面积，透射电镜观察骨骼肌线粒体变化，Western blot检测PGC1α、AMPKα、p-AMPKα及SIRT1等的表达，并比较老年鼠与成年鼠的表达差异。

结果

①与自由进食组比较，热量限制组骨骼肌衰减指数变化不明显，胫前肌等肌纤维密度显著升高 (

0.01)，相对横截面积降低 (

0.01)；②电镜观察显示：与自由进食组比较，热量限制组骨骼肌线粒体长度和宽度均增加 (

0.05，

0.01)，相对密度增加 (

0.01)，PGC1α表达升高 (

0.05)；③与自由进食组比较，热量限制组骨骼肌AMPK的磷酸化水平升高 (

0.01)，同时SIRT1表达也升高 (

0.05)；④与成年鼠比较，老年鼠骨骼肌AMPK磷酸化水平下降 (

0.05)，SIRT1和PGC1α的表达也均下降 (

0.05)。

结论

热量限制能显著促进老化进程中骨骼肌线粒体的生成及活性，这一作用可能通过激活AMPK信号途径实现。

Abstract

Objective

To observe the effects of calorie restriction (CR) on the biological characteristics of mouse skeletal muscle mitochondria during the aging process

and explore the molecular mechanism of the biological effects of CR.

Methods

Thirty C57BL/6 male mice

13 months old

were randomly divided into 2 groups: free eating (ad libitum

AL) group and CR group

and the CR group was fed with 60% consumption of the AL group. After 12 weeks of CR

the sarcopenia index of skeletal muscle

and the myofiber density and cross section area in tibialis anterior muscle were measured. The changes of skeletal muscle mitochondria were observed with transmission electron microscopy. The expression levels of AMPKα

p-AMPKα

SIRT1

and PGC1α were detected by Western blotting

and those of AMPKα and SIRT1 in the normal adult mice and aged mice were compared.

Results

Compared with the AL group

the sarcopenia index did not change significantly

the myofiber density was increased significantly (

0.01)

and the relative cross-sectional area was decreased (

0.01) in the CR group. Electron microscope observation showed that the length and width of skeletal muscle mitochondria in the CR group were significantly increased (

0.05

0.01)

the relative density was significantly increased (

0.01)

and the expression of PGC1α was significantly increased (

0.05). The phosphorylation of AMPK in skel

etal muscle was enhanced by CR

and the expression levels of SIRT1 and PGC1α were significantly increased (

0.05). Compared with the normal adult mice

the phosphorylation of AMPK and the expression of SIRT1 and PGC1α in the aged mice were significantly decreased (

0.05).

Conclusion

CR can significantly promote the biogenesis and activity of mitochondria in the aging skeletal muscle

which may be regulated by activating AMPK signaling pathway.

关键词

Keywords

references

Rizza W, Veronese N, Fontana L. What are the roles of calorie restriction and diet quality in promoting healthy longevity[J]. Ageing Res Rev, 2014, 13: 38-45. DOI:10.1016/j.arr.2013.11.002

Mattison J A, Roth G S, Beasley T M, et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study[J]. Nature, 2012, 489(7415): 318-321. DOI:10.1038/nature11432

López-Lluch G, Navas P. Calorie restriction as an intervention in ageing[J].JPhysiol (Lond), 2016, 594(8): 2043-2060. DOI:10.1113/JP270543

Argilés J M, Campos N, Lopez-Pedrosa J M, et al. Skeletal muscle regulates metabolism via interorgan crosstalk: roles in health and disease[J].JAm Med Dir Assoc, 2016, 17(9): 789-796. DOI:10.1016/j.jamda.2016.04.019

Mckiernan S H, Colman R J, Lopez M, et al. Caloric restriction delays aging-induced cellular phenotypes in rhesus monkey skeletal muscle[J]. Exp Gerontol, 2011, 46(1): 23-29. DOI: 10.1016/j.exger.2010.09.011

McKiernan S H, Colman R J, Aiken E, et al. Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys[J]. Exp Gerontol, 2012, 47(3): 229-236. DOI:10.1016/j.exger.2011.12.009

Mckiernan S H, Bua E, Mcgorray J, et al. Early-onset calorie restriction conserves fiber number in aging rat skeletal muscle[J]. FASEB J, 2004, 18(3): 580-581. DOI: 10.1096/fj.03-0667fje

HardieDG, RossFA, HawleySA. AMPK:anutrient and energy sensor that maintains energy homeostasis[J]. Nat Rev Mol Cell Biol, 2012, 13(4): 251-262. DOI:10.1038/nrm3311

Cantó C, Auwerx J. Calorie restriction: is AMPKakey sensor and effector[J]. Physiology (Bethesda), 2011, 26(4): 214-224. DOI:10.1152/physiol.00010.2011

Donati A, Cavallini G, Bergamini E. Methods for inducing and monitoring liver autophagy relative to aging and antiaging caloric restriction in rats[J]. Meth Enzymol, 2009, 452: 441-455. DOI:10.1016/S0076-6879(08)03626-4

Ning Y C, Cai G Y, Zhuo L, et al. Beneficial effects of short-term calorie restriction against cisplatin-induced acute renal injury in aged rats[J]. Nephron Exp Nephrol, 2013, 124(3/4): 19-27. DOI:10.1159/000357380

Marzetti E, LeesHA, WohlgemuthSE, et al. Sarcopenia of aging: underlying cellular mechanisms and protection by calorie restriction[J]. Biofactors, 2009, 35(1): 28-35. DOI:10.1002/biof.5

Marzetti E, Calvani R, Cesari M, et al. Mitochondrial dysfunction and sarcopenia of aging: from signaling pathways to clinical trials[J]. IntJBiochem Cell Biol, 2013, 45(10): 2288-2301. DOI:10.1016/j.biocel.2013.06.024

Sharples A P, Hughes D C, Deane C S, et al. Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake[J]. Aging Cell, 2015, 14(4): 511-523. DOI:10.1111/acel.12342

Burkewitz K, Zhang Y, MairWB. AMPK at the nexus of energetics and aging[J]. Cell Metab, 2014, 20(1): 10-25. DOI:10.1016/j.cmet.2014.03.002

Rodgers J T, Lerin C, Gerhart-Hines Z, et al. Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways[J]. FEBS Lett, 2008, 582(1): 46-53. DOI:10.1016/j.febslet.2007.11.034

Tang B L. Sirt1 and the Mitochondria[J]. Mol Cells, 2016, 39(2): 87-95. DOI:10.14348/molcells.2016.2318

Lam Y Y, Peterson C M, Ravussin E. Resveratrol vs. calorie restriction: data from rodents to humans[J]. Exp Gerontol, 2013, 48(10): 1018-1024. DOI:10.1016/j.exger.2013.04.005

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