Adiponectin receptor PAQR-2 signaling senses low temperature to promote C. elegans longevity by regulating autophagy

Abstract

Temperature is a key factor for determining the lifespan of both poikilotherms and homeotherms. It is believed that animals live longer at lower body temperatures. However, the precise mechanism remains largely unknown. Here, we report that autophagy serves as a boost mechanism for longevity at low temperature in the nematode Caenorhabditis elegans . The adiponectin receptor AdipoR2 homolog PAQR-2 signaling detects temperature drop and augments the biosynthesis of two ω-6 polyunsaturated fatty acids, γ-linolenic acid and arachidonic acid. These two polyunsaturated fatty acids in turn initiate autophagy in the epidermis, delaying an age-dependent decline in collagen contents, and extending the lifespan. Our findings reveal that the adiponectin receptor PAQR-2 signaling acts as a regulator linking low temperature with autophagy to extend lifespan, and suggest that such a mechanism may be evolutionally conserved among diverse organisms.

Post-Translational Protein Deimination Signatures in Serum and Serum-Extracellular Vesicles of Bos taurus Reveal Immune, Anti-Pathogenic, Anti-Viral, Metabolic and Cancer-Related Pathways for Deimination

“…The adipocytokine signalling pathway has key regulatory roles in metabolism and glucose regulation [170][171][172][173] and is linked to a range of pathologies, including type II diabetes and insulin resistance [174], to myopathies [175] and cancer [176]. Adiponectin has also been linked to longevity [177] and to regenerative functions [178]. In the cow, adiponectin is a known glycoprotein and has been assessed in bovine tissues as well as body fluids [179] and amongst other been identified as a pro-survival signal in ER stress in the mammary gland [180].…”

Leveraging a gain-of-function allele of Caenorhabditis elegans paqr-1 to elucidate membrane homeostasis by PAQR proteins

“…paqr-2 and iglr-2 single and double mutants have the same phenotypes, including a characteristic tail tip defect and intolerance to cold and dietary saturated fatty acids (SFAs) [16,31]. Additionally, the paqr-2 mutant, and presumably the iglr-2 mutant as well, also exhibits several phenotypes secondary to its primary membrane homeostasis defect, including defects in lifespan [30], vitellogenin trafficking [15], brood size [30], locomotion [30], autophagy [32] and proteostasis [33]. These phenotypes are secondary to the primary membrane fluidity defects of paqr-2 and iglr-2 mutants because they can be suppressed fully or partially by low, fluidizing concentrations of mild detergents [18], by providing supplements of unsaturated fatty acids [16,18], or by secondary mutations that increase the relative abundance of unsaturated fatty acids (UFAs) among phospholipids, such as mdt- 15 (et14), nhr- 49(et8), fld-1(et48) and several others [14,17,18].…”

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

“…It has received considerable interest in the field of metabolic and obesity research (Frankenberg et al, 2017;Spracklen et al, 2019), as well as in diabetes (Yamauchi et al, 2003), due to its key function in regulating glucose (Yamauchi et al, 2002). Adiponectin is furthermore linked to longevity (Chen et al, 2019a(Chen et al, , 2019b, regenerative functions (Fiaschi et al, 2014) and has roles in myopathies, such as Duchenne muscular dystrophy and collagen VI-related myopathies (Gamberi et al, 2019). Adiponectin is also implicated in a range of cancers, often in relation to obesity (Parida et al, 2019).…”

“…Mutations in desmoplakin have been linked to multiple allergies, severe dermatitis and metabolic wasting (SAM) syndrome (Liang et al, 2019). It is also linked to Carvajal syndrome, involving altered skin and hair abnormalities, and heart diseases (Yermakovich et al, 2018), including cardiomyopathies (Reichl et al, 2018;Chen et al, 2019aChen et al, , 2019b. Desmosomal proteins have been shown to have both tumourpromoting and tumour-suppressive functions, depending of cancer types and can regulate cell proliferation, differentiation, migration, apoptosis, and impact treatment sensitivity in different types of cancers (Zhou et al, 2017).…”