Calorie restriction and sirtuins revisited

Guarente, Leonard

doi:10.1101/gad.227439.113

Cited by 394 publications

(309 citation statements)

References 200 publications

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“…Many lines of evidence indicate that sirtuins mediate the effects of CR, and small molecule SIRT1 activators confer broad health benefits likely through SIRT1‐mediated deacetylation of target proteins [reviewed in Ref. Guarente, 2013]. Overall, our findings are in agreement with the role of CYB5R3 and NQO1 as efficient intracellular generators of NAD + for utilization by sirtuins (Ross & Siegel, 2017; Shen et al., 2017), and are consistent with the notion that modulation of SIRT1 and NAD + levels represents a promising approach for the treatment of age‐associated metabolic diseases (Herranz et al., 2010; Imai, 2010; Verdin, 2015).…”

Section: Discussionsupporting

confidence: 88%

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

et al. 2018

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SummaryCalorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH‐dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b 5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age‐associated diseases. However, it is unclear whether changes in metabolic homeostasis solely through upregulation of these NADH‐dehydrogenases have a positive impact on health and survival. We generated a mouse that overexpresses both metabolic enzymes leading to phenotypes that resemble aspects of CR including a modest increase in lifespan, greater physical performance, a decrease in chronic inflammation, and, importantly, protection against carcinogenesis, one of the main hallmarks of CR. Furthermore, these animals showed an enhancement of metabolic flexibility and a significant upregulation of the NAD +/sirtuin pathway. The results highlight the importance of these NAD + producers for the promotion of health and extended lifespan.

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Section: Discussionsupporting

confidence: 88%

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

et al. 2018

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“…Calorie restriction (CR), a dietary regimen that reduce 30-40% in intake, is reported to be the most robust way to prevent organ insufficiency, 27,28) however it is difficult to keep strictly within the limit of calorie restriction method in daily life. Therefore, development of calorie restriction mimetics is desperately needed.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Protects against High-Fat Diet Induced Renal Pathological Damage and Cell Senescence by Activating SIRT1

Zhang

et al. 2016

Biological & Pharmaceutical Bulletin

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Obesity-related renal diseases have been a worldwide issue. Effective strategy that prevents high fat-diet induced renal damage is of great significance. Resveratrol, a natural plant polyphenol, is famous for its antioxidant activity, cardioprotective effects and anticancer properties. However whether resveratrol can play a role in the treatment of renal diseases is unknown. In this study, we added resveratrol in normal glucose or high glucose medium and provide evidences that resveratrol protects against high-glucose triggered oxidative stress and cell senescence. Moreover, mice were fed with standard diet, standard diet plus resveratrol, high-fat diet or high-fat diet plus resveratrol for 3 months, and results show that resveratrol treatment prevents high-fat diet induced renal pathological damage by activating SIRT1, a key member in the mammalian sirtuin family that response to calorie restriction life-extension method. This research confirms the potential role of resveratrol in the treatment of renal diseases and may provide an effective and convenient method to mimic the beneficial effects of calorie restriction.

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“…SIRT1 is a nicotinamide adenine dinucleotide (NAD+)‐dependent deacetylase that catalyzes the removal of acetyl groups from lysine residues on histone proteins, resulting in gene silencing (Braunstein, Rose, Holmes, Allis, & Broach, 1993; Imai, Armstrong, Kaeberlein, & Guarente, 2000; Tanny, Dowd, Huang, Hilz, & Moazed, 1999). SIRT1 also deacetylates transcription factors including PGC1α, which induces mitochondrial oxidative phosphorylation (Lagouge et al, 2006), p53, which promotes cell survival (Luo et al, 2001; Vaziri et al, 2001) and triggers adaptation to calorie restriction with its accompanying stress resistance (Guarente, 2013). Through these actions, SIRT1 functions to maintain cellular homeostasis and thereby prevent age‐related pathological changes.…”

Section: Introductionmentioning

confidence: 99%

SIRT1 deacetylase in aging‐induced neuromuscular degeneration and amyotrophic lateral sclerosis

et al. 2018

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SIRT1 is an NAD+‐dependent deacetylase that functions in a variety of cells and tissues to mitigate age‐associated diseases. However, it remains unknown if SIRT1 also acts to prevent pathological changes that accrue in motor neurons during aging and amyotrophic lateral sclerosis (ALS). In this study, we show that SIRT1 expression decreases in the spinal cord of wild‐type mice during normal aging. Using mouse models either overexpressing or lacking SIRT1 in motor neurons, we found that SIRT1 slows age‐related degeneration of motor neurons’ presynaptic sites at neuromuscular junctions (NMJs). Transcriptional analysis of spinal cord shows an overlap of greater than 90% when comparing alterations during normal aging with changes during ALS, revealing a substantial upregulation in immune and inflammatory response genes and a downregulation of synaptic transcripts. In addition, overexpressing SIRT1 in motor neurons delays progression to end‐stage disease in high copy SOD1G93A mice. Thus, our findings suggest that there are parallels between ALS and aging, and interventions to impede aging may also slow the progression of this devastating disease.

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Calorie restriction and sirtuins revisited

Cited by 394 publications

References 200 publications

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

Resveratrol Protects against High-Fat Diet Induced Renal Pathological Damage and Cell Senescence by Activating SIRT1

SIRT1 deacetylase in aging‐induced neuromuscular degeneration and amyotrophic lateral sclerosis

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Calorie restriction and sirtuins revisited

Cited by 394 publications

References 200 publications

Overexpression of CYB5R3 and NQO1, two NAD+‐producing enzymes, mimics aspects of caloric restriction

Overexpression of CYB5R3 and NQO1, two NAD+‐producing enzymes, mimics aspects of caloric restriction

Resveratrol Protects against High-Fat Diet Induced Renal Pathological Damage and Cell Senescence by Activating SIRT1

SIRT1 deacetylase in aging‐induced neuromuscular degeneration and amyotrophic lateral sclerosis

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Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction