Dataset Information

Age-Associated Changes of Sirtuin 2 Expression in CNS and the Periphery.

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.

SUBMITTER: Garmendia-Berges M

PROVIDER: S-EPMC10741187 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Age-Associated Changes of Sirtuin 2 Expression in CNS and the Periphery.

Garmendia-Berges Maider M Sola-Sevilla Noemi N Mera-Delgado MCarmen M Puerta Elena E

Biology 20231129 12

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 lev ...[more]

PMID: 38132302

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Project description:Neurons producing serotonin (5-hydroxytryptamine, 5-HT) constitute one of the most widely distributed neuronal networks in the mammalian central nervous system (CNS) and exhibit a profuse innervation throughout the CNS already at early stages of development. Serotonergic neuron specification is controlled by a combination of secreted molecules and transcription factors such as Shh, Fgf4/8, Nkx2.2, Lmx1b and Pet1. In the mouse, Pet1 mRNA expression appears between 10 and 11 days post coitum (dpc) in serotonergic post-mitotic precursors and persists in serotonergic neurons up to adulthood, where it promotes the expression of genes defining the mature serotonergic phenotype such as tryptophan hydroxylase 2 (Tph2) and serotonin transporter (SERT). Hence, the generation of genetic tools based on Pet1 specific expression represents a valuable approach to study the development and function of the serotonergic system. Here, we report the generation of a Pet1(210)-Cre transgenic mouse line in which the Cre recombinase is expressed under the control of a 210 kb fragment from the Pet1 genetic locus to ensure a reliable and faithful control of somatic recombination in Pet1 cell lineage. Besides Cre-mediated recombination accurately occurred in the serotonergic system as expected and according to previous studies, Pet1(210)-Cre transgenic mouse line allowed us to identify novel, so far uncharacterized, Pet1 expression domains. Indeed, we showed that in the raphe Pet1 is expressed also in a non-serotonergic neuronal population intermingled with Tph2-expressing cells and mostly localized in the B8 and B9 nuclei. Moreover, we detected Cre-mediated recombination also in the developing pancreas and in the ureteric bud derivatives of the kidney, where it reflected a specific Pet1 expression. Thus, Pet1(210)-Cre transgenic mouse line faithfully drives Cre-mediated recombination in all Pet1 expression domains representing a valuable tool to genetically manipulate serotonergic and non-serotonergic Pet1 cell lineages.

Dataset Information

Age-Associated Changes of Sirtuin 2 Expression in CNS and the Periphery.

Publications

Age-Associated Changes of Sirtuin 2 Expression in CNS and the Periphery.

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