Mammalian Sirtuins: Biological Insights and Disease Relevance

By M. Haigis, D. Sinclair. Annual Review of Pathology, 2010

2,040 citations recorded by the source corpus.

Aging is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as type II diabetes mellitus, neurodegenerative diseases, cancer, and cardiovascular disease. Historically, researchers have focused on investigating individual pathways in isolated organs as a strategy to identify the root cause of a disease, with hopes of designing better drugs. Studies of aging in yeast led to the discovery of a family of conserved enzymes known as the sirtuins, which affect multiple pathways that increase the life span and the overall health of organisms. Since the discovery of the first known mammalian sirtuin, SIRT1, 10 years ago, there have been major advances in our understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span. This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years.

Subfields: Epidemiology, Geriatrics and Gerontology, Physiology

View Paper: https://www.semanticscholar.org/paper/cbfad45b325afc31c2d00a0f7e0b7f9cf5b10f58

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Citations in the corpus

NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism (2018, background): “SIRTs utilize NAD as a substrate to catalyze the deacetylation reaction at lysine residue of proteins to produce NAM, deacetylated protein, and 2¢-O-acetyl-ADP ribose (24, 57, 66).”
SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function (2012, background): “…sirtuins (SIRT1-7) are a conserved family of NAD+-dependent deacetylases and ADP-ribosyltransferases involved in numerous fundamental cellular processes including gene silencing, DNA repair, and metabolic regulation (Baur et al., 2010; Donmez and Guarente, 2010; Haigis and Sinclair, 2010).”
Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. (2013, background): “Sir2 (silent information regulator 2) family proteins, now called ‘‘sirtuins,’’ have been demonstrated to coordinate metabolic responses to changes in nutritional availability and maintain physiological homeostasis in mammals (Haigis and Sinclair, 2010).”
In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming (2016, positive): “…of DNA damage, increased ROS production, telomere shortening, cellular senescence, and defects in nuclear envelope architecture (Bernardes de Jesus and Blasco, 2013; Guarente, 2008; Haigis and Sinclair, 2009; Kennedy and Lamming, 2016; Soul-toukis and Partridge, 2016; Steffen and Dillin, 2016).”
The Role of Sirtuins in Antioxidant and Redox Signaling (2017, background): “Due to the essential roles SIRT6 has in cellular homeostasis, disruption of this enzyme appears to produce an effect on disease development (12, 53, 57, 101, 136, 161).”
Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA non-homologous end-joining (2010, positive): “Class III HDACs, also known as sirtuins, are NAD dependent and consist of SIRT1–SIRT7, which are closely related to the yeast Sir2 protei”
Sirtuins as regulators of metabolism and healthspan (2012, background): “Sirtuins have received significant attention since the discovery that the yeast sirtuin silent information regulator 2 (Sir2), which was originally described as a regulator of transcriptional silencing of mating-type loci, telomeres and ribosomal DNA (reviewed in Ref”