Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging

Zhou, Jin; Chong, Shu Yun; Lim, Andrea; Singh, Brijesh Kumar; Sinha, Rohit Anthony; Salmon, Adam B.; Yen, Paul M.

doi:10.18632/aging.101181

Cited by 108 publications

(97 citation statements)

References 45 publications

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“…Aging. Autophagy is an important cellular process involved in aging and longevity that gradually declines during cardiac aging, resulting in an increase in the sensitivity of the heart to stress [24]. Autophagy is a catabolic process involved in lifespan and aging in the cardiovascular system [25].…”

Section: Autophagy In Cardiacmentioning

confidence: 99%

Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging

Quan

Xin

Tian

et al. 2020

Oxidative Medicine and Cellular Longevity

132

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Mitochondrial DNA (mtDNA) damage is associated with the development of cardiovascular diseases. Cardiac aging plays a central role in cardiovascular diseases. There is accumulating evidence linking cardiac aging to mtDNA damage, including mtDNA mutation and decreased mtDNA copy number. Current wisdom indicates that mtDNA is susceptible to damage by mitochondrial reactive oxygen species (mtROS). This review presents the cellular and molecular mechanisms of cardiac aging, including autophagy, chronic inflammation, mtROS, and mtDNA damage, and the effects of mitochondrial biogenesis and oxidative stress on mtDNA. The importance of nucleoid-associated proteins (Pol γ), nuclear respiratory factors (NRF1 and NRF2), the cGAS-STING pathway, and the mitochondrial biogenesis pathway concerning the development of mtDNA damage during cardiac aging is discussed. Thus, the repair of damaged mtDNA provides a potential clinical target for preventing cardiac aging.

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Section: Autophagy In Cardiacmentioning

confidence: 99%

Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging

Quan

Xin

Tian

et al. 2020

Oxidative Medicine and Cellular Longevity

132

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“…Total RNA isolation from cultured cells and liver tissue was performed using InviTrap Spin Universal RNA kit (Stratec Biomedical, Birkenfeld, Germany), and RT-qPCR was performed as described previously [54] using QuantiTect SYBR Green PCR kit and KiCqStart SYBR Green optimized primers from Sigma-Aldrich (KSPQ12012).…”

Section: Mrna Expression Analysis By Reverse Transcription-quantitatimentioning

confidence: 99%

Development of an in vitro senescent hepatic cell model for metabolic studies in aging

Singh

Tripathi

Yen

et al. 2020

Preprint

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Although in vitro senescence models have been developed using primary fibroblasts, they may not be applicable for the study of metabolically active organs such as the liver. We thus developed an in vitro protocol to induce senescence in AML12 nontransformed hepatocyte cell lines derived from mice transgenic for transforming growth factor alpha. Sequential oxidative stress with hydrogen peroxide induced premature senescence in these cells as they exhibited molecular and metabolic signatures, had increased SA-Gal and H2A.X staining, and elevated senescence and pro-inflammatory gene expression that resembled the livers from aged mice.Metabolic phenotyping showed fuel switching towards more glycolysis, mitochondrial glutamine oxidation, and impaired energy production that also was similar to the livers from aged mice. Additionally, Senescence Activated Secretory Proteins (SASPs) sensitized normal AML12 cells to palmitate-induced toxicity, a known pathological effect of hepatic aging. In summary, we have generated an in vitro senescent AML12 cell model that not only show the molecular hallmarks of aging, but also recapitulates the aberrant metabolic phenotype found in aged liver. As such, they represent a novel and useful model to study nutritional, pharmacological, or genetic factors on hepatic metabolism during aging.

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“…Interestingly, studies have found that macroautophagy capacity seems to decline with age, as indicated by lower levels of autophagy biomarkers, such as Atg7 and LC3‐II/I ratio, and an increase in protein levels of p62 and Bnip3 in aged mice and humans . Similar to muscle specific Atg7 knockout mice, it is possible that age‐related muscle atrophy is not necessarily due to impaired macroautophagy in skeletal muscles, but compensatory response, such as apoptosis, promoted by the impairment of autophagy.…”

Section: The Mammalian Target Of Rapamycin (Mtor)/protein Kinase B (Amentioning

confidence: 99%

Sarcopenia: Tilting the Balance of Protein Homeostasis

2019

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Sarcopenia, defined as age‐associated decline of muscle mass and function, is a risk factor for mortality and disability, and comorbid with several chronic diseases such as type II diabetes and cardiovascular diseases. Clinical trials showed that nutritional supplements had positive effects on muscle mass, but not on muscle function and strength, demonstrating our limited understanding of the molecular events involved in the ageing muscle. Protein homeostasis, the equilibrium between protein synthesis and degradation, is proposed as the major mechanism underlying the development of sarcopenia. As the key central regulator of protein homeostasis, the mammalian target of rapamycin (mTOR) is proposed to be essential for muscle hypertrophy. Paradoxically, sustained activation of mTOR complex 1 (mTORC1) is associated with a loss of sensitivity to extracellular signaling in the elderly. It is not understood why sustained mTORC1 activity, which should induce muscle hypertrophy, instead results in muscle atrophy. Here, recent findings on the implications of disrupting protein homeostasis on muscle physiology and sarcopenia development in the context of mTOR/protein kinase B (AKT) signaling are reviewed. Understanding the role of these molecular mechanisms during the ageing process will contribute towards the development of targeted therapies that will improve protein metabolism and reduce sarcopenia.

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Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging

Cited by 108 publications

References 45 publications

Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging

Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging

Development of an in vitro senescent hepatic cell model for metabolic studies in aging

Sarcopenia: Tilting the Balance of Protein Homeostasis

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