G protein-coupled receptors that influence lifespan of human and animal models

Abstract

Humanity has always sought to live longer and for this, multiple strategies have been tried with varying results. In this sense, G protein-coupled receptors (GPCRs) may be a good option to try to prolong our life while maintaining good health since they have a substantial participation in a wide variety of processes of human pathophysiology and are one of the main therapeutic targets. In this way, we present the analysis of a series of GPCRs whose activity has been shown to affect the lifespan of animal and human models, and in which we put a special interest in describing the molecular mechanisms involved. Our compilation of data revealed that the mechanisms most involved in the role of GPCRs in lifespan are those that mimic dietary restriction, those related to insulin signaling and the AMPK and TOR pathways, and those that alter oxidative homeostasis and severe and/or chronic inflammation. We also discuss the possibility of using agonist or antagonist drugs, depending on the beneficial or harmful effects of each GPCR, in order to prolong people's lifespan and healthspan.

SIRT7 in the aging process

“…Consistent with the known roles of sirtuins in aging and life extension, several studies have established a close relationship between SIRT7 and age-related processes [ 34 , 39 ] (Fig. 2 ).…”

Correlated evolution of social organization and lifespan in mammals

“…Among them, the hormones-related pathway "G-protein-coupled receptors (GPCRs), class B secretin-like" was positively associated with both solitary living and longevity, but negatively associated with group living (polysel: solitary, score = 6.18, P = 4.71 × 10 −2 ; group-living, score = −6.04, P = 3.96 × 10 −2 ; longevity, score = 7.15, P = 3.83 × 10 −2 ). The secretin-like family of GPCRs include receptors for polypeptide hormones, such as secretin, parathyroid hormone and vasoactive intestinal peptide, which play vital roles in physiological homeostasis, nervous diseases, the stress response and longevity [52][53][54] . Acting as a catalyst in steroid hormone synthesis 55 , the cytochrome P450-related pathway has been enriched ("drug metabolism -cytochrome P450", polysel: pair-living, score = 18.52, P = 1.40 × 10 −4 ; longevity, score = 16.00 ± 0.04, P = 0.02 ± 1.06 × 10 −3 ).…”

Fas (CD95)/FasL (CD178) system during ageing

“…Exercise and diet are considered the cornerstone of almost all healthy ageing programmes, and it has been observed that people who exercise regularly and eat properly not only live longer, but also live better (Figure 5) (Lagunas‐Rangel, 2022a, 2022a, 2022b). It has been reported that daily swimming or moderate running exercise can reduce activation of the Fas/FasL system in the hippocampus and left ventricle of d ‐galactose‐aged rats and thereby decrease age‐induced brain and cardiac apoptosis (Lay et al, 2021; Li et al, 2016; Lin et al, 2020).…”