Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence.

Noemi Sola-Sevilla,Maria S Aymerich,Ana Ricobaraza,Ruben Hernandez-Alcoceba,Rosa M Tordera,Elena Puerta

doi:10.3390/ijms22063107

Noemi Sola-Sevilla, Maria S Aymerich + Show 4 more

Open Access

https://doi.org/10.3390/ijms22063107

Copy DOI

Abstract

Sirtuin 2 (SIRT2) has been associated to aging and age-related pathologies. Specifically, an age-dependent accumulation of isoform 3 of SIRT2 in the CNS has been demonstrated; however, no study has addressed the behavioral or molecular consequences that this could have on aging. In the present study, we have designed an adeno-associated virus vector (AAV-CAG-Sirt2.3-eGFP) for the overexpression of SIRT2.3 in the hippocampus of 2 month-old SAMR1 and SAMP8 mice. Our results show that the specific overexpression of this isoform does not induce significant behavioral or molecular effects at short or long term in the control strain. Only a tendency towards a worsening in the performance in acquisition phase of the Morris Water Maze was found in SAMP8 mice, together with a significant increase in the pro-inflammatory cytokine Il-1β. These results suggest that the age-related increase of SIRT2.3 found in the brain is not responsible for induction or prevention of senescence. Nevertheless, in combination with other risk factors, it could contribute to the progression of age-related processes. Understanding the specific role of SIRT2 on aging and the underlying molecular mechanisms is essential to design new and more successful therapies for the treatment of age-related diseases.

Highlights

It has been demonstrated that Sirt2 gene expression is significantly repressed with age in hematopoietic stem cells (HSCs) [35]
In agreement with this result, Luo et al recently showed that there is a reduction in Sirt2 expression together with an increase in mitochondrial stress in aged HSCs, which leads to an activation of NOD, LRR, and pyrin domain-containing protein 3 (NLRP3) inflammasome [36]
The in vivo and in vitro evidence presented above suggest that Sirtuin 2 (SIRT2) seems to be a crucial regulator of aging and age-related pathologies; controversial findings have been published on its specific role in these processes