Monoterpenes as Sirtuin-1 Activators: Therapeutic Potential in Aging and Related Diseases

Abstract

Sirtuin 1 (SIRT) is a class III, NAD+-dependent histone deacetylase that also modulates the activity of numerous non-histone proteins through deacylation. SIRT1 plays critical roles in regulating and integrating cellular energy metabolism, response to stress, and circadian rhythm by modulating epigenetic and transcriptional regulation, mitochondrial homeostasis, proteostasis, telomere maintenance, inflammation, and the response to hypoxia. SIRT1 expression and activity decrease with aging, and enhancing its activity extends life span in various organisms, including mammals, and improves many age-related diseases, including cancer, metabolic, cardiovascular, neurodegenerative, respiratory, musculoskeletal, and renal diseases, but the opposite, that is, aggravation of various diseases, such as some cancers and neurodegenerative diseases, has also been reported. Accordingly, many natural and synthetic SIRT1 activators and inhibitors have been developed. Known SIRT1 activators of natural origin are mainly polyphenols. Nonetheless, various classes of non-polyphenolic monoterpenoids have been identified as inducers of SIRT1 expression and/or activity. This narrative review discusses current information on the evidence that supports the role of those compounds as SIRT1 activators and their potential both as tools for research and as pharmaceuticals for therapeutic application in age-related diseases.

Molecular Mechanisms Underlying the Anti-Inflammatory Properties of (R)-(-)-Carvone: Potential Roles of JNK1, Nrf2 and NF-κB

“…Therefore, they are considered promising targets for the development of therapeutic strategies to halt or, at least, slow down the progression of those diseases. In this regard, many natural compounds have been found to have positive effects in in vitro and in vivo models of many diseases by inhibiting those processes [ 8 , 9 , 34 ] and/or activating anti-inflammatory pathways such as Nrf2 and SIRT1 [ 35 , 36 , 37 ]. The results obtained in this study suggest that (R)-(-)-carvone may be useful by targeting the interaction between inflammatory and anti-inflammatory/antioxidant signaling pathways and intermediates.…”

Roles of Aging, Circular RNAs, and RNA Editing in the Pathogenesis of Amyotrophic Lateral Sclerosis: Potential Biomarkers and Therapeutic Targets

“…Increased expression of circFOXO3 is involved in cellular senescence in the CNS, which may lead to neurodegeneration; however, a controversial report has shown that expression levels of circFOXO3 are significantly decreased in the blood of elderly persons and in late passage primary culture cells [51]. CircPVT1, a circular form of an exon of PVT1, influences cellular senescence and neurodegeneration by changing the expression levels of let-7 and miR-199-5a: let-7 regulates immune response, autophagy, and apoptosis [52][53][54], whereas miR199-5a regulates the expression levels of sirtuin1 (SIRT1) mRNA, which is associated with brain aging and neurodegeneration resulting from the dysregulation of mitochondrial energy metabolism [55][56][57][58]. Epigenetic modifications, such as DNA and RNA methylation, influence chromatin function, and their age-related changes are associated with brain aging and neurodegeneration [14].…”