From Ancient Pathways to Aging Cells—Connecting Metabolism and Cellular Senescence

Wiley, Christopher D.; Campisi, Judith

doi:10.1016/j.cmet.2016.05.010

Cited by 338 publications

(315 citation statements)

References 91 publications

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“…A subtype of senescence is driven by mitochondrial dysfunction that is termed mitochondrial dysfunction‐induced senescence (MIDAS). [ 46,47 ] Studies on how the metabolome of senescent cells contributes to this cell‐state has led to insights on the role of NAD + as a central metabolic node in senescence. Nacarelli et.al.…”

Section: Application Of Metabolomics For Biomarker Discovery In Agingmentioning

confidence: 99%

The Aging Metabolome—Biomarkers to Hub Metabolites

Sharma

Ramanathan

2020

Proteomics

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Aging biology is intimately associated with dysregulated metabolism, which is one of the hallmarks of aging. Aging‐related pathways such as mTOR and AMPK, which are major targets of anti‐aging interventions including rapamcyin, metformin, and exercise, either directly regulate or intersect with metabolic pathways. In this review, numerous candidate bio‐markers of aging that have emerged using metabolomics are outlined. Metabolomics studies also reveal that not all metabolites are created equally. A set of core “hub” metabolites are emerging as central mediators of aging. The hub metabolites reviewed here are nicotinamide adenine dinucleotide, reduced nicotinamide dinucleotide phosphate, α‐ketoglutarate, and β‐hydroxybutyrate. These “hub” metabolites have signaling and epigenetic roles along with their canonical roles as co‐factors or intermediates of carbon metabolism. Together these hub metabolites suggest a central role of the TCA cycle in signaling and metabolic dysregulation associated with aging.

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Section: Application Of Metabolomics For Biomarker Discovery In Agingmentioning

confidence: 99%

The Aging Metabolome—Biomarkers to Hub Metabolites

Sharma

Ramanathan

2020

Proteomics

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“…oncogene-induced senescence: Ras activation inhibits the expression of key dNTP enzymes, leading to replication stress and in turn inducing the senescent response (Aird et al, 2013;Mannava et al, 2013;Wiley & Campisi, 2016). oncogene-induced senescence: Ras activation inhibits the expression of key dNTP enzymes, leading to replication stress and in turn inducing the senescent response (Aird et al, 2013;Mannava et al, 2013;Wiley & Campisi, 2016).…”

Section: Yap Overcomes Blockade Of Dntp Metabolism During Oncogeneindmentioning

confidence: 99%

d NTP metabolism links mechanical cues and YAP / TAZ to cell growth and oncogene‐induced senescence

et al. 2018

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YAP/TAZ, downstream transducers of the Hippo pathway, are powerful regulators of cancer growth. How these factors control proliferation remains poorly defined. Here, we found that YAP/TAZ directly regulate expression of key enzymes involved in deoxynucleotide biosynthesis and maintain dNTP precursor pools in human cancer cells. Regulation of deoxynucleotide metabolism is required for YAP-induced cell growth and underlies the resistance of YAP-addicted cells to chemotherapeutics targeting dNTP synthesis. During RAS-induced senescence, YAP/TAZ bypass RAS-mediated inhibition of nucleotide metabolism and control senescence. Endogenous YAP/TAZ targets and signatures are inhibited by RAS/MEK1 during senescence, and depletion of YAP/TAZ is sufficient to cause senescence-associated phenotypes, suggesting a role for YAP/TAZ in suppression of senescence. Finally, mechanical cues, such as ECM stiffness and cell geometry, regulate senescence in a YAP-dependent manner. This study indicates that YAP/TAZ couples cell proliferation with a metabolism suited for DNA replication and facilitates escape from oncogene-induced senescence. We speculate that this activity might be relevant during the initial phases of tumour progression or during experimental stem cell reprogramming induced by YAP.

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“…Cellular senescence is characterized by the permanent arrest of cell proliferation, induction of the senescence-associated secretory phenotype (SASP), and selective degradation of specific proteins by the ubiquitin-proteosome pathway [33, 34]. Cellular senescence may be induced by multiple metabolic, cellular, and genotoxic stressors such as excessive ROS, DNA damage, oncogene activation, short telomeres, low NAD+/NADPH ratios, dysfunctional mitochondria, autophagy inhibition, and decreased ribosome biogenesis.…”

Section: Molecular Mechanisms Of Agingmentioning

confidence: 99%

Sirtuins and Accelerated Aging in Scleroderma

Wyman

Atamas

2018

Curr Rheumatol Rep

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Purpose of Review Premature activation of aging-associated molecular mechanisms is emerging as an important contributor to many diseases, including scleroderma. Among central regulators of the aging process are a group of histone deacetylases called sirtuins (SIRTs). Recent findings implicate these molecules as pathophysiological players in scleroderma skin and lung fibrosis. The goal of this article is to review recent studies on the involvement of SIRTs in scleroderma from the perspective of aging-related molecular mechanisms. Recent Findings Despite a degree of controversy in this rapidly developing field, the majority of data suggest that SIRT levels are decreased in tissues from patients with scleroderma compared to healthy controls as well as in animal models of scleroderma. Molecular studies reveal several mechanisms through which declining SIRT levels contribute to fibrosis, with the most attention given to modulation of the TGF-β signaling pathway. Activation of SIRTs in cell culture and in animal models elicits antifibrotic effects. Summary Declining SIRT levels and activity are emerging as pathophysiological contributors to scleroderma. Restoration of SIRTs may be therapeutic in patients with scleroderma.

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From Ancient Pathways to Aging Cells—Connecting Metabolism and Cellular Senescence

Cited by 338 publications

References 91 publications

The Aging Metabolome—Biomarkers to Hub Metabolites

The Aging Metabolome—Biomarkers to Hub Metabolites

d NTP metabolism links mechanical cues and YAP / TAZ to cell growth and oncogene‐induced senescence

Sirtuins and Accelerated Aging in Scleroderma

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