Quality control systems in cardiac aging

Quarles, Ellen; Dai, Dao Fu; Tocchi, Autumn; Basisty, Nathan; Gitari, Lemuel; Rabinovitch, Peter S.

doi:10.1016/j.arr.2015.02.003

Cited by 33 publications

(42 citation statements)

References 237 publications

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“…The importance of SIRT7 for the heart muscle is related to its role in the regulation of mitochondrial function [8], control of p-53-dependent apoptosis of cardiomyocytes and stress responses [6], including the response to acute cardiovascular injury in mice [21]. Thus, SIRT7 could prevent the aging-associated deterioration of cardiac muscle function [22,23,24]. …”

Section: Discussionmentioning

confidence: 99%

Age-Related Changes in Sirtuin 7 Expression in Calorie-Restricted and Refed Rats

et al. 2015

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Background: Sirtuins (SIRT1-7) have been implicated to mediate the beneficial effects of calorie restriction for healthy aging. While the physiological functions of SIRT7 are still poorly understood, SIRT7 has recently been shown to affect ribosome biogenesis, mitochondrial gene expression, and hepatic lipid metabolism. Objective: To analyze the effects of age and short-term calorie restriction (SCR) and subsequent refeeding on SIRT7 expression in key metabolic tissues. Methods: Four- and 24-month-old male Wistar rats were subjected to 40% SCR for 30 days, followed by ad libitum feeding for 2 or 4 days. Liver, white adipose tissue (WAT), heart and skeletal muscle samples were analyzed by real-time PCR and Western blotting for SIRT7 mRNA and protein expression, respectively. Results: Aging had diverse effects on SIRT7 levels in lipogenic tissues: both the mRNA and protein levels increased in the retroperitoneal depot (rWAT), did not change in the epididymal depot (eWAT), and decreased in the subcutaneous depot (sWAT) and the liver of old as compared to young animals. In the heart, extensor digitorum longus muscle (EDL) and soleus muscle (SOL), Sirt7 gene but not protein expression was lower in old than in young control rats. SCR did not affect SIRT7 expression in WAT and the liver in both age groups. In the heart of young animals, SCR did not affect SIRT7 mRNA or protein level. In EDL, SIRT7 protein but not mRNA levels decreased after SCR and remained reduced upon refeeding. In SOL, both SIRT7 mRNA and protein expression were inhibited by refeeding. In old rats, cardiac Sirt7 expression increased after SCR and refeeding. In old rats' EDL and SOL muscles, SIRT7 protein expression was inhibited by refeeding. Conclusion: Age-related changes of SIRT7 gene expression in key organs of energy homeostasis are tissue dependent.

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Section: Discussionmentioning

confidence: 99%

Age-Related Changes in Sirtuin 7 Expression in Calorie-Restricted and Refed Rats

et al. 2015

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“…Induction of autophagy is commonly thought to be the main effec tor in calorific restriction. However, calorific restric tion is not feasible in most humans, because it requires a life long reduction in calorie intake of ≥20%, while maintaining proper intake of minerals and vitamins 167 . In addition to calorific restriction, exercise also reduces the risk of cardiovascular diseases and has been pro posed to slow cardiac ageing 131 .…”

Section: Calorific Restriction and Exercisementioning

confidence: 99%

Proteostasis in cardiac health and disease

Henning

Brundel²

2017

Nat Rev Cardiol

132

111

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The worldwide increase in life expectancy gives rise to an increasing prevalence of cardiac diseases, which remain the leading cause of disability and death in the developed world [1][2][3] . Currently, the mechanisms under lying how ageing contributes to the initiation or acceler ation of cardiac diseases are essentially unresolved. Prevailing theories of ageing centre on gradual derail ment of cellular protein homeostasis -proteostasis -either by design (genetically) or by 'wear and tear' (environmentally) 3 . Central to the role of proteostasis derailment as a major factor in ageing is the observation that protein function declines over time.Proteins are the most versatile and complex macro molecules and are involved in the proper functioning of every biological process 4 . After synthesis as a poly peptide chain from the genetic code, proper function of a protein relies heavily on its correct folding into a 3D native state and on various post translational modifi cations, mostly involving the addition of chem ical groups (including phosphate, acetate, and carbo hydrate). Protein maturation, transport, and ultimately breakdown is monitored and supported by various classes of proteins, collectively called 'protein quality control' (PQC) [3][4][5] . Balanced proteostasis, therefore, depends on proper PQC and is crucial for cellular and organismal health 6 . The intricate network making up the PQC involves numerous proteins, of which the main players are the chaperones and their regula tors 4,7-9 (assisting in folding and refolding of proteins) and the pathways that clear irreversibly misfolded and aggregation prone proteins (the ubiquitin-proteasome system [UPS] and autophagy systems) 9-11 . With ageing, the gradual accumulation of misfolded or damaged pro teins, together with concomitant failure of PQC, results in proteotoxic stress and compromised defence against reactive oxygen species (ROS) 10 , a process that is likely to be accelerated in various age related diseases includ ing neurodegenerative diseases 12,13 , type 2 diabetes mel litus 14 , cancer 15 , and cardiac diseases [16][17][18][19][20] . In addition to the accumulation of misfolded proteins, ageing is accompanied by an imbalance in the proteome, as indi cated by lowered expression of chaperone, proteaso mal, ribosomal, and mitochondrial proteins, whereas proteins related to oxidative stress are upregulated 21,22 . Although mild impairment of proteostasis extends lifespan in Caenorhabditis elegans, referred to as hormesis, sustained impairment is accompanied by loss of PQC to neutralize this effect 3,5 . Importantly, evidence indicates that the amount of soluble, aggregate prone protein oligomers, rather than the abundance of pro tein aggregates, correlates with disease severity 23,24 . Therefore, protein aggregates, which contain both misfolded proteins and elevated levels of chaper ones, constitute an adequate PQC response, aimed at sequestering potentially harmful protein oligomers, rather than embodying the ultimate cellular threat 25 . This ...

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“…This process indeed occurs in the heart. Of special relevance is that aging causes dysregulation of nutrient sensing, with abnormal metabolism and mitochondrial (Mito) dysfunction [5][6][7]. Though some studies have suggested that Reactive Oxygen Species (ROS) production may be implicated in the aging process, the role of ROS as a primary cause of cellular senescence has also been questioned [6,8].…”

Section: Aging and Decreased Cardiac Functionmentioning

confidence: 99%

“…The process of general aging-related changes in model organisms has been explored recently [5][6][7]. The rate of aging is a controlled process governed by epigenetic pathways and biochemical processes which are conserved in evolution [6].…”

Section: Aging and Decreased Cardiac Functionmentioning

confidence: 99%

Metabolic Syndrome in Aging Heart: Molecular Insights

Díaz-Juárez¹,

Pastelín²,

Suárez³

2017

J Metabolic Synd

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Risk factors that define the metabolic syndrome (MetS) develop with age increasing its prevalence. Therefore, MetS can be considered an age-related health problem. Mechanism involved in aging and MetS are incompletely understood. The goal of this review is to highlight novel molecular maladaptive mechanism that tiger cardiac disease and common in aging and MetS. We focus on mitochondrial energetic function as well as mitochondrial calcium handling. In addition, we analyzed the role of O-GlcNAcylation which is a posttranslational modification that triggers multiple signaling pathways.

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Quality control systems in cardiac aging

Cited by 33 publications

References 237 publications

Age-Related Changes in Sirtuin 7 Expression in Calorie-Restricted and Refed Rats

Age-Related Changes in Sirtuin 7 Expression in Calorie-Restricted and Refed Rats

Proteostasis in cardiac health and disease

Metabolic Syndrome in Aging Heart: Molecular Insights

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