Caloric restriction and cellular senescence

Fontana, Luigi; Nehme, Jamil; Demaria, Marco

doi:10.1016/j.mad.2018.10.005

Cited by 76 publications

(48 citation statements)

References 90 publications

(94 reference statements)

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“…The spectrum of cell senescence has been widened by studies showing that post-mitotic neurons may also display a senescent phenotype that can be ameliorated by a hypocaloric diet [107]. The mechanisms by which caloric restriction may reduce the appearance of new senescent cells include a reduction of ROS from nutrient metabolism, stimulation of autophagy, increased expression of sirtuins, and enhancement of normal DDR mechanisms [108]. At the organismal level, caloric restriction leads to reductions in bioavailable IGF-1 [109], a known inducer of cellular senescence over the long term [66].…”

Section: How Can We Fight Cellular Senescence?mentioning

confidence: 99%

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review

et al. 2020

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Life expectancy has increased substantially over the last few decades, leading to a worldwide increase in the prevalence and burden of agingassociated diseases. Recent evidence has proven that cellular senescence contributes substantially to the development of these disorders. Cellular senescence is a state of cell cycle arrest with suppressed apoptosis and concomitant secretion of multiple bioactive factors (the senescence-associated secretory phenotype-SASP) that plays a physiological role in embryonic development and healing processes. However, DNA damage and oxidative stress that occur during aging cause the accumulation of senescent cells, which through their SASP bring about deleterious effects on multiple organ and systemic functions. Ablation of senescent cells through genetic or pharmacological means leads to improved life span and health span in animal models, and preliminary evidence suggests it may also have a positive impact on human health. Thus, strategies to reduce or eliminate the burden of senescent cells or their products have the potential to impact multiple clinical outcomes with a single intervention. In this review, we touch upon the basics of cell senescence and summarize the current state of development of therapies against cell senescence for human use.

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Section: How Can We Fight Cellular Senescence?mentioning

confidence: 99%

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review

et al. 2020

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“…However, the molecular mechanisms underlying the beneficial effects of CR on ARHL remain incompletely understood. Metabolic alterations by stimulating metabolic regulator proteins such as SIRT1, AMP‐activated protein kinase (AMPK), and PPARγ coactivator‐1α (PGC‐1α), which occur as part of the adaptation to CR, potentially underlie the efficacy of CR (Fontana, Nehme, & Demaria, ). These observations suggest that alterations of mitochondrial energy metabolism play a critical role in CR response.…”

Section: Introductionmentioning

confidence: 99%

“…These observations suggest that alterations of mitochondrial energy metabolism play a critical role in CR response. In fact, CR has been shown to protect mitochondrial function from age‐dependent decline, reduce mtDNA damage, reverse many changes in mitochondrial gene expression, and cause metabolic changes to increase energy metabolism, delaying aging in mammals (Fontana et al, ).…”

Section: Introductionmentioning

confidence: 99%

Augmentation of cellular NAD⁺ by NQO1 enzymatic action improves age‐related hearing impairment

Kim

Cao

Oh³

et al. 2019

Aging Cell

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Age‐related hearing loss (ARHL) is a major neurodegenerative disorder and the leading cause of communication deficit in the elderly population, which remains largely untreated. The development of ARHL is a multifactorial event that includes both intrinsic and extrinsic factors. Recent studies suggest that NAD+/NADH ratio may play a critical role in cellular senescence by regulating sirtuins, PARP‐1, and PGC‐1α. Nonetheless, the beneficial effect of direct modulation of cellular NAD+ levels on aging and age‐related diseases has not been studied, and the underlying mechanisms remain obscure. Herein, we investigated the effect of β‐lapachone (β‐lap), a known plant‐derived metabolite that modulates cellular NAD+ by conversion of NADH to NAD+ via the enzymatic action of NADH: quinone oxidoreductase 1 (NQO1) on ARHL in C57BL/6 mice. We elucidated that the reduction of cellular NAD+ during the aging process was an important contributor for ARHL; it facilitated oxidative stress and pro‐inflammatory responses in the cochlear tissue through regulating sirtuins that alter various signaling pathways, such as NF‐κB, p53, and IDH2. However, augmentation of NAD+ by β‐lap effectively prevented ARHL and accompanying deleterious effects through reducing inflammation and oxidative stress, sustaining mitochondrial function, and promoting mitochondrial biogenesis in rodents. These results suggest that direct regulation of cellular NAD+ levels by pharmacological agents may be a tangible therapeutic option for treating various age‐related diseases, including ARHL.

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“…Previous studies demonstrated that DR delayed cancer progression in humans and experimental models by decreasing the rate of aging [50,51]. DR induced FGF21 and AMPK, protecting from aging-related cell dysfunction and exhibiting anti-inflammatory and antitumorigenic properties.…”

Section: Discussionmentioning

confidence: 99%

Dietary Restriction Suppresses Steatosis-Associated Hepatic Tumorigenesis in Hepatitis C Virus Core Gene Transgenic Mice

et al. 2020

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Background and Aims: Dietary restriction (DR) is a preventive strategy for obesity, metabolic syndrome, cardiovascular disease, and diabetes. Although an interconnection between obesity, metabolic syndrome, fatty liver, and hepatocellular carcinoma has been documented, the mechanism and impact of DR on steatosis-derived hepatocarcinogenesis are not fully understood. This study aimed to evaluate whether DR can prevent hepatic tumorigenesis. Methods: Male hepatitis C virus core gene transgenic (HCVcpTg) mice that develop spontaneous age-dependent insulin resistance, hepatic steatosis, and ensuing liver tumor development without apparent hepatic fibrosis, were fed with either a control diet ad libitum (control group) or 70% of the same control diet (DR group) for 15 months, and liver phenotypes were investigated. Results: DR significantly reduced the number and volume of liver tumors. DR attenu

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Caloric restriction and cellular senescence

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Cited by 76 publications

References 90 publications

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review

Augmentation of cellular NAD⁺ by NQO1 enzymatic action improves age‐related hearing impairment

Dietary Restriction Suppresses Steatosis-Associated Hepatic Tumorigenesis in Hepatitis C Virus Core Gene Transgenic Mice

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Caloric restriction and cellular senescence

Abstract: Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Cited by 76 publications

References 90 publications

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review

Augmentation of cellular NAD+ by NQO1 enzymatic action improves age‐related hearing impairment

Dietary Restriction Suppresses Steatosis-Associated Hepatic Tumorigenesis in Hepatitis C Virus Core Gene Transgenic Mice

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Augmentation of cellular NAD⁺ by NQO1 enzymatic action improves age‐related hearing impairment