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Updated: Jul 7, 2025
Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
Published on: February 27, 2016
Age-Associated Changes of Sirtuin 2 Expression in CNS and the Periphery
Maider Garmendia-Berges1, Noemi Sola-Sevilla1,2, MCarmen Mera-Delgado1
1Pharmaceutical Sciences Department, Division of Pharmacology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
Abstract:
Sirtuin 2 (SIRT2), one of the seven members of the sirtuin family, has emerged as a potential regulator of aging and age-related pathologies since several studies have demonstrated that it shows age-related changes in humans and different animal models. A detailed analysis of the relevant works published to date addressing this topic shows that the changes that occur in SIRT2 with aging seem to be opposite in the brain and in the periphery. On the one hand, aging induces an increase in SIRT2 levels in the brain, which supports the notion that its pharmacological inhibition is beneficial in different neurodegenerative diseases. However, on the other hand, in the periphery, SIRT2 levels are reduced with aging while keeping its expression is protective against age-related peripheral inflammation, insulin resistance, and cardiovascular diseases. Thus, systemic administration of any known modulator of this enzyme would have conflicting outcomes. This review summarizes the currently available information on changes in SIRT2 expression in aging and the underlying mechanisms affected, with the aim of providing evidence to determine whether its pharmacological modulation could be an effective and safe pharmacological strategy for the treatment of age-related diseases.
Insights
Sirtuin 2 (SIRT2) levels change oppositely in the brain and periphery during aging. This review explores SIRT2
Area of Science:
- Biochemistry
- Gerontology
- Neuroscience
Background:
- Sirtuin 2 (SIRT2) is implicated in aging and age-related diseases.
- SIRT2 exhibits age-related expression changes in humans and animal models.
- Opposing roles of SIRT2 in the brain and periphery during aging are suggested.
Purpose of the Study:
- To review age-related changes in SIRT2 expression.
- To analyze underlying mechanisms affected by SIRT2.
- To evaluate SIRT2's potential as a therapeutic target for age-related diseases.
Main Methods:
- Literature review of studies on SIRT2 and aging.
- Analysis of age-dependent changes in SIRT2 expression.
- Examination of SIRT2's role in neurodegeneration, inflammation, and metabolic diseases.
Main Results:
- Aging increases SIRT2 levels in the brain, suggesting benefits from inhibition in neurodegenerative diseases.
- Aging decreases SIRT2 levels in the periphery, where its maintenance protects against inflammation, insulin resistance, and cardiovascular issues.
- Systemic SIRT2 modulation may yield conflicting therapeutic outcomes due to tissue-specific effects.
Conclusions:
- SIRT2's dual role in aging necessitates cautious therapeutic strategies.
- Understanding tissue-specific SIRT2 regulation is crucial for treating age-related conditions.
- Further research is needed to determine safe and effective pharmacological modulation of SIRT2 for age-related diseases.
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