Recent progress in the biology and physiology of sirtuins

By Toren Finkel, C. Deng, R. Mostoslavsky. Nature, 2009

1,517 citations recorded by the source corpus.

The sirtuins are a highly conserved family of NAD+-dependent enzymes that regulate lifespan in lower organisms. Recently, the mammalian sirtuins have been connected to an ever widening circle of activities that encompass cellular stress resistance, genomic stability, tumorigenesis and energy metabolism. Here we review the recent progress in sirtuin biology, the role these proteins have in various age-related diseases and the tantalizing notion that the activity of this family of enzymes somehow regulates how long we live.

Subfields: Epidemiology, Geriatrics and Gerontology, Physiology

View Paper: https://www.semanticscholar.org/paper/98259064b8fb9020129074d5e0388a491d952830

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. W. Kaelin
2. S. McKnight
3. R. DePinho
4. Ergun Sahin
5. Matt Kaeberlein
6. G. Shadel
7. Brian K. Kennedy
8. V. Longo

In Geriatrics and Gerontology

1. S. McKnight
2. W. Kaelin
3. E. Verdin
4. M. Haigis
5. V. Longo
6. Brian K. Kennedy
7. R. DePinho
8. Ergun Sahin

In Physiology

1. W. Kaelin
2. S. McKnight
3. E. Verdin
4. M. Haigis
5. R. DePinho
6. Ergun Sahin
7. Matt Kaeberlein
8. G. Shadel

Citations in the corpus

• THE HISTONE DEACETYLASE SIRT6 IS A NOVEL TUMOR SUPPRESSOR THAT CONTROLS CANCER METABOLISM (2012, positive): “Given their absolute dependency on NAD, sirtuins have evolved as critical modulators of stress responses, DNA repair, and metabolism, sensing changes in metabolic cues in order to exert adaptive responses (Finkel et al., 2009).”
• SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways (2013, background): “Sirtuin family NAD+-dependent Lys deacetylases regulate key biological processes in mammals, including many aspects of metabolism (Finkel et al., 2009).”
• Cross-regulation of Signaling and Immune Responses by IFN-γ and STAT1 (2009, background): “Sirtuin1, is regulated by the overall cellular metabolic state as reflected in the NAD/NADH ratio and can be selectively and therapeutically modulated by small molecule compounds (Finkel et al., 2009).”
• Replicative and Chronological Aging in Saccharomyces cerevisiae (2012, positive): “Sirtuins have been extensively studied in recent years for their potential role as conserved modulators of aging in a variety of organisms, including mammals (Finkel et al., 2009).”
• SIRT3 is a Mitochondrial Localized Tumor Suppressor Required for Maintenance of Mitochondrial Integrity and Metabolism During Stress (2010, background): “The incidence of human malignancies increases exponentially as a function of aging, suggesting a mechanistic connection between aging (longevity) and carcinogenesis (Finkel et al., 2009).”
• SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization (2011, background): “Sirtuins are a conserved family of NAD-dependent ADP-ribosyltransferases and/or protein deacetylases involved in metabolism, stress response, and longevity (Finkel et al., 2009).”
• Transcriptional and Epigenetic Mechanisms of Addiction (2011, background): “For example, sirtuins deacetylate several transcription factors such as forkhead box O (FOXO) proteins or NF-κB, and serve scaffolding functions by contributing to transcriptional repressive complexe”
• Linking functional decline of telomeres, mitochondria and stem cells during ageing (2010, positive): “Second, it explains why mice lacking SIRT1 or SIRT6 — proteins that attenuate p53 activity — develop premature agein”
• SIRT3 Deficiency and Mitochondrial Protein Hyperacetylation Accelerate the Development of the Metabolic Syndrome (2011, positive): “(E and F) mRNA transcript levels were quantified by qPCR from WT mice fed a SD or HFD overexpressing adenoviral PGC-1a or GFP as a control (*p < 0.05, **p < 0.01, n = 5/condition, ± SEM). including metabolic homeostasis (for a review, see Finkel et al., 2009).”
• The Role of Sirtuins in Antioxidant and Redox Signaling (2017, background): “In addition to playing important roles in chromatin regulation and recruitment of transcription factors such as NF-jB, SIRT6 has also been suggested to have critical functions in other cellular processes such as gene expression, glucose homeostasis, and DNA repair (40, 64, 94, 160, 161).”
• Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-related Hearing Loss under Caloric Restriction (2010, background): “Sirtuins are NAD-dependent protein deacetylases that regulate life span in lower organisms and have emerged as broad regulators of cellular fate and mammalian physiology (Donmez and Guarente, 2010; Finkel et al., 2009).”
• Influence of Metabolism on Epigenetics and Disease (2013, positive): “The latter proteins are members of the sirtuin family of deacetylases (Figure 1), which include two isoforms that are primarily housed in the nuclei of mammalian cells (SIRT6 and SIRT7), three that are localized to mitochondria (SIRT3, SIRT4, and SIRT5), and two that are found in both cytoplasmic an”