Sirtuins, Aging, and Medicine

Guarente, Leonard

doi:10.1056/nejmra1100831

Cited by 477 publications

(391 citation statements)

References 91 publications

(91 reference statements)

Supporting

Mentioning

388

Contrasting

Unclassified

Order By: Relevance

“…The sirtuins are a highly conserved family of NAD ϩ -dependent deacetylases that have been shown to increase lifespan in lower organisms. Mammals have seven sirtuins (SIRT1-7) (16). Of the seven sirtuins, SIRT1, SIRT2, SIRT6, and SIRT7 are located in the nucleus (33).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sirtuin 1 Is a Negative Regulator of Parathyroid Hormone Stimulation of Matrix Metalloproteinase 13 Expression in Osteoblastic Cells

Fei

Shimizu

McBurney³

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Parathyroid hormone (PTH) stimulates MMP13 in osteoblasts. Results: Sirtuin 1 (SIRT1) activation suppresses PTH stimulation of Mmp13 expression, and this process is mediated by the AP-1 complex. Conclusion: SIRT1 is a novel suppressor of PTH stimulation of MMP13 expression. Significance: Activation of SIRT1 and suppression of MMP13 may prolong the anabolic bone-forming period of PTH treatment in osteoporotic patients.

show abstract

Section: Discussionmentioning

confidence: 99%

“…SIRT1 is one of the class III HDACs, being an NAD ϩ -dependent protein deacetylase. Mammals have seven sirtuins (SIRT1-7) (16). Of the seven sirtuins, SIRT1 has been the most investigated.…”

Section: Parathyroid Hormone (Pth)mentioning

confidence: 99%

Sirtuin 1 Is a Negative Regulator of Parathyroid Hormone Stimulation of Matrix Metalloproteinase 13 Expression in Osteoblastic Cells

Fei

Shimizu

McBurney³

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In mammals there are seven sirtuin paralogs. SIRT1, SIRT6, and SIRT7 are nuclear proteins, SIRT3, SIRT4, and SIRT5 are imported into mitochondria, and SIRT2 is principally cytoplasmic (Finkel et al 2009;Haigis and Sinclair 2010;Verdin et al 2010;Guarente 2011). Through their deacylation activities, sirtuins modulate the biological activities of a wide array of target pathways.…”

Section: Sirtuin Proteinsmentioning

confidence: 99%

Mitochondrial Biogenesis through Activation of Nuclear Signaling Proteins

Dominy

Puigserver

2013

Cold Spring Harbor Perspectives in Biology

207

171

View full text Add to dashboard Cite

“…In fact, using the above-described “molecular age” assay and focusing on a family of genes with phylogenetically-conserved age-modulatory roles (i.e. sirtuins, 74 ), we have reported that subjects carrying a low-expressing polymorphism of the Sirtuin 5 gene had molecular ages that were older than actual chronological age, as measured in the cingulate cortex of human postmortem samples. 57 We further showed that this effect was accompanied by expression changes for a set of genes whose products are localized to the mitochondria, including PINK-1 and DJ-1, two Parkinson's disease-associated genes, in ways that would promote mitochondrial dysfunction-related diseases, including the age-gated Parkinson's disease.…”

Section: Molecular Brain Aging: An Etiological Role In Lld?mentioning

confidence: 99%

The Age-by-Disease Interaction Hypothesis of Late-Life Depression

McKinney

Sibille

2013

The American Journal of Geriatric Psychiatry

View full text Add to dashboard Cite

The phenomenological diagnosis of depression is successful in increasing diagnostic reliability, but it is a classification scheme without biological bases. One subtype of depression for which evidence suggests a unique biological basis is late-life depression (LLD), with first onset of symptoms after the age of 65. LLD is common and poses a significant burden on affected individuals, caretakers, and society. The pathophysiology of LLD includes disruptions of the neural network underlying mood, which can be conceptualized as the result of dysfunction in multiple underlying biological processes. Here, we briefly review current LLD hypotheses and then describe the characteristics of molecular brain aging and their overlap with disease processes. Further, we propose a new hypothesis for LLD, the Age-by-Disease Interaction hypothesis, which posits that the clinical presentation of LLD is the integrated output of specific biological processes that are pushed in LLD-promoting directions by changes in gene expression naturally occurring during brain aging, hence leading the brain to a physiological state that is more susceptible to LLD, since additional pushes by genetic, environmental and biochemical factors may now be sufficient to generate dysfunctional states that produce depressive symptoms. We put our propositions together into a decanalization model to aid in illustrating how age-related biological changes of the brain can shift the repertoire of available functional states in a pro-depression direction, and how additional factors can readily lead the system into distinct and stable maladaptive phenotypes, including LLD. This model brings together basic research on neuropsychiatric and neurodegenerative diseases more closely with the investigation of normal aging. Specifically, identifying biological processes affected during normal aging may inform the development of new interventions for the prevention and treatment of LLD.

show abstract

Sirtuins, Aging, and Medicine

Abstract: Register to receive weekly e-mail messages with the latest job openings that match your specialty, as well as preferred geographic region, practice setting, call schedule, and more. Visit the NEJM CareerCenter at NEJMjobs.org for more information.

Cited by 477 publications

References 91 publications

Sirtuin 1 Is a Negative Regulator of Parathyroid Hormone Stimulation of Matrix Metalloproteinase 13 Expression in Osteoblastic Cells

Sirtuin 1 Is a Negative Regulator of Parathyroid Hormone Stimulation of Matrix Metalloproteinase 13 Expression in Osteoblastic Cells

Mitochondrial Biogenesis through Activation of Nuclear Signaling Proteins

The Age-by-Disease Interaction Hypothesis of Late-Life Depression

Contact Info

Product

Resources

About