Long-term caloric restriction activates the myocardial SIRT1/AMPK/PGC-1α pathway in C57BL/6J male mice

Ma, Lina; Wang, Rong; Wang, Hongjuan; Zhang, Yaxin; Zhao, Zhigang

doi:10.29219/fnr.v64.3668

Cited by 26 publications

(21 citation statements)

References 45 publications

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“…106 , 107 In general, caloric restriction activates both SIRT1, PGC-1α, and AMPK in parallel, and the molecular actions of AMPK support those of SIRT1/PGC-1α and oppose those of Akt/mTOR with respect to cellular homeostasis and survival ( Figure 2 ). In addition, the actions of AMPK and SIRT1/PGC-1α reinforce each other 93 ; the effect of AMPK to promote NAD+ leads to SIRT1 activation, 108 and AMPK can activate PGC-1α by phosphorylation. 109 Simultaneously, SIRT1 can augment the activity of upstream regulators of AMPK, 110 while inhibition of AMPK leads to suppression of PGC-1α.…”

Section: Sirt1 and Akt/mtor Signalling In The Regulation Of Organismamentioning

confidence: 89%

“… 109 Simultaneously, SIRT1 can augment the activity of upstream regulators of AMPK, 110 while inhibition of AMPK leads to suppression of PGC-1α. 93 In addition, AMPK can inhibit mTOR by an action on its upstream regulators as well as through a direct effect on components of the mTORC1 complex. 111 , 112 As a result of the interplay of these effects, AMPK augments the ability of SIRT1/PGC-1α signalling to oppose the actions of the Akt/mTOR pathway.…”

Section: Sirt1 and Akt/mtor Signalling In The Regulation Of Organismamentioning

confidence: 99%

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Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure

Packer

2020

European Heart Journal

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The two primary molecular regulators of lifespan are sirtuin-1 (SIRT1) and mammalian target of rapamycin complex 1 (mTORC1). Each plays a central role in two highly interconnected pathways that modulate the balance between cellular growth and survival. The activation of SIRT1 [along with peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) and adenosine monophosphate-activated protein kinase (AMPK)] and the suppression of mTORC1 (along with its upstream regulator, Akt) act to prolong organismal longevity and retard cardiac ageing. Both activation of SIRT1/PGC-1α and inhibition of mTORC1 shifts the balance of cellular priorities so as to promote cardiomyocyte survival over growth, leading to cardioprotective effects in experimental models. These benefits may be related to direct actions to modulate oxidative stress, organellar function, proinflammatory pathways, and maladaptive hypertrophy. In addition, a primary shared benefit of both SIRT1/PGC-1α/AMPK activation and Akt/mTORC1 inhibition is the enhancement of autophagy, a lysosome-dependent degradative pathway, which clears the cytosol of dysfunctional organelles and misfolded proteins that drive the ageing process by increasing oxidative and endoplasmic reticulum stress. Autophagy underlies the ability of SIRT1/PGC-1α/AMPK activation and Akt/mTORC1 suppression to extend lifespan, mitigate cardiac ageing, alleviate cellular stress, and ameliorate the development and progression of cardiomyopathy; silencing of autophagy genes abolishes these benefits. Loss of SIRT1/PGC-1α/AMPK function or hyperactivation of Akt/mTORC1 is a consistent feature of experimental cardiomyopathy, and reversal of these abnormalities mitigates the development of heart failure. Interestingly, most treatments that have been shown to be clinically effective in the treatment of chronic heart failure with a reduced ejection fraction have been reported experimentally to exert favourable effects to activate SIRT1/PGC-1α/AMPK and/or suppress Akt/mTORC1, and thereby, to promote autophagic flux. Therefore, the impairment of autophagy resulting from derangements in longevity gene signalling is likely to represent a seminal event in the evolution and progression of cardiomyopathy.

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Section: Sirt1 and Akt/mtor Signalling In The Regulation Of Organismamentioning

confidence: 89%

Section: Sirt1 and Akt/mtor Signalling In The Regulation Of Organismamentioning

confidence: 99%

Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure

Packer

2020

European Heart Journal

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“…In addition, LANCL1 overexpression in both L6 cells and the SM from LANCL2 −/− mice elicits an increased transcription of Sirt1 and NAMPT ( Figure 3 , Figure 6 C). The AMPK/PGC-1α/Sirt1 axis is implicated in several pivotal functions in SM, including mitochondrial biogenesis and fusion, conservation of muscle contractility and recovery of muscle function caused by disuse or ageing [ 20 ], and protection of muscle cells from apoptosis induced by nutrient deprivation or ischemia-reperfusion injury [ [27] , [28] , [29] ]. The overexpression of NAMPT in SM improves physical endurance in mice [ 24 ] and maintains mitochondrial NAD + levels, membrane potential, respiration, and cell survival to oxidative stress [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

LANCL1 binds abscisic acid and stimulates glucose transport and mitochondrial respiration in muscle cells via the AMPK/PGC-1α/Sirt1 pathway

Spinelli

Begani

Guida

et al. 2021

Molecular Metabolism

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Objective Abscisic acid (ABA) is a plant hormone also present and active in animals. In mammals, ABA regulates blood glucose levels by stimulating insulin-independent glucose uptake and metabolism in adipocytes and myocytes through its receptor LANCL2. The objective of this study was to investigate whether another member of the LANCL protein family, LANCL1, also behaves as an ABA receptor and, if so, which functional effects are mediated by LANCL1. Methods ABA binding to human recombinant LANCL1 was explored by equilibrium-binding experiments with [ 3 H]ABA, circular dichroism, and surface plasmon resonance. Rat L6 myoblasts overexpressing either LANCL1 or LANCL2, or silenced for the expression of both proteins, were used to investigate the basal and ABA-stimulated transport of a fluorescent glucose analog (NBDG) and the signaling pathway downstream of the LANCL proteins using Western blot and qPCR analysis. Finally, glucose tolerance and sensitivity to ABA were compared in LANCL2 −/− and wild-type (WT) siblings. Results Human recombinant LANCL1 binds ABA with a K d between 1 and 10 μM, depending on the assay (i.e., in a concentration range that lies between the low and high-affinity ABA binding sites of LANCL2). In L6 myoblasts, LANCL1 and LANCL2 similarly, i) stimulate both basal and ABA-triggered NBDG uptake (4-fold), ii) activate the transcription and protein expression of the glucose transporters GLUT4 and GLUT1 (4-6-fold) and the signaling proteins AMPK/PGC-1α/Sirt1 (2-fold), iii) stimulate mitochondrial respiration (5-fold) and the expression of the skeletal muscle (SM) uncoupling proteins sarcolipin (3-fold) and UCP3 (12-fold). LANCL2 −/− mice have a reduced glucose tolerance compared to WT. They spontaneously overexpress LANCL1 in the SM and respond to chronic ABA treatment (1 μg/kg body weight/day) with an improved glycemia response to glucose load and an increased SM transcription of GLUT4 and GLUT1 (20-fold) of the AMPK/PGC-1α/Sirt1 pathway and sarcolipin, UCP3, and NAMPT (4- to 6-fold). Conclusions LANCL1 behaves as an ABA receptor with a somewhat lower affinity for ABA than LANCL2 but with overlapping effector functions: stimulating glucose uptake and the expression of muscle glucose transporters and mitochondrial uncoupling and respiration via the AMPK/PGC-1α/Sirt1 pathway. Receptor redundancy may have been advantageous in animal evolution, given the role of the ABA/LANCL system in the insulin-independent stimulation of cell glucose uptake and energy metabolism.

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“…Diminished status of cellular energy leads to lower mitochondrial activity and consequently lower aerobic respiration, increased adenosine monophosphate / adenosine triphosphate (AMP/ATP) ratio, and increased nicotinamide adenine dinucleotide (NAD+) levels. Further, two cellular nutrient and energy sensors, adenosine monophosphate kinase (AMPK) and sirtuin 1 deacetylase (SIRT1) are activated [92][93][94]. Activated AMPK induces a series of events resulting in reduced fatty acid synthesis, oxidation, and cholesterol synthesis, but active SIRT1 may increase ketogenesis and lipolysis, and decrease glycolysis.…”

Section: Epigenetic Link Between Nutrition Aging and Cancermentioning

confidence: 99%

Nutrition in Cancer Therapy in the Elderly—An Epigenetic Connection?

et al. 2020

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The continuous increase in life expectancy results in a steady increase of cancer risk, which consequently increases the population of older adults with cancer. Older adults have their age-related nutritional needs and often suffer from comorbidities that may affect cancer therapy. They frequently are malnourished and present advanced-stage cancer. Therefore, this group of patients requires a special multidisciplinary approach to optimize their therapy and increase quality of life impaired by aging, cancer, and the side effects of therapy. Evaluation strategies, taking advantage of comprehensive geriatric assessment tools, including the comprehensive geriatric assessment (CGA), can help individualize treatment. As epigenetics, an emerging element of the regulation of gene expression, is involved in both aging and cancer and the epigenetic profile can be modulated by the diet, it seems to be a candidate to assist with planning a nutritional intervention in elderly populations with cancer. In this review, we present problems associated with the diet and nutrition in the elderly undergoing active cancer therapy and provide some information on epigenetic aspects of aging and cancer transformation. Nutritional interventions modulating the epigenetic profile, including caloric restriction and basal diet with modifications (elimination diet, supplementary diet) are discussed as the ways to improve the efficacy of cancer therapy and maintain the quality of life of older adults with cancer.

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Long-term caloric restriction activates the myocardial SIRT1/AMPK/PGC-1α pathway in C57BL/6J male mice

Cited by 26 publications

References 45 publications

Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure

Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure

LANCL1 binds abscisic acid and stimulates glucose transport and mitochondrial respiration in muscle cells via the AMPK/PGC-1α/Sirt1 pathway

Nutrition in Cancer Therapy in the Elderly—An Epigenetic Connection?

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