Recent Progress in Regulation of Aging by Insulin/IGF-1 Signaling in Caenorhabditis elegans

Abstract

Caenorhabditis elegans has been used as a major model organism to identify genetic factors that regulate organismal aging and longevity. Insulin/insulin-like growth factor 1 (IGF- 1) signaling (IIS) regulates aging in many species, ranging from nematodes to humans. C. elegans is a nonpathogenic genetic nematode model, which has been extensively utilized to identify molecular and cellular components that function in organismal aging and longevity. Here, we review the recent progress in the role of IIS in aging and longevity, which involves direct regulation of protein and RNA homeostasis, stress resistance, metabolism and the activities of the endocrine system. We also discuss recently identified genetic factors that interact with canonical IIS components to regulate aging and health span in C. elegans. We expect this review to provide valuable insights into understanding animal aging, which could eventually help develop anti-aging drugs for humans.

Keywords: Caenorhabditis elegans; aging; health span; homeostasis; insulin/IGF-1 signaling; longevity.

Fig. 1. Summary of recent progress in the roles of insulin/IGF-1 signaling (IIS) in C. elegans longevity.

Reduced IIS promotes longevity by enhancing cellular maintenance, including proteostasis, via increasing autophagy and lysosome activities, RNA homeostasis, through regulating nonsense-mediated mRNA decay (NMD) and microRNAs (miRNAs), and oxidative stress and pathogen resistance. IIS also regulates aging by modulating lipid and amino acid metabolism, endocrine signaling among several tissues, including the intestine, neurons and muscles, and the activities of novel factors that interact with classical IIS components. These processes cooperatively contribute to longevity. The roles of the genes in aging regulation shown in this figure are discussed in the corresponding sections of the text more in detail. unc-120/serum response factor, chn-1/C-term of Hsp70-interacting protein (CHIP), prx-5/peroxisomal biogenesis factor 5 (PEX5), smg-2/UPF1, algn-2/alpha-1,3/1,6-mannosyltransferase (ALG2), rgs-1/regulator of G protein signaling 20 (RGS20), zip-10/bZIP transcription factor, adipose triglyceride lipase-1 (atgl-1), forkhead transcription factor-9 (fkh-9), spr-3/4/repressor element-1 silencing transcription factor (REST), initiation factor (EIF)-2α (eif-2α), cyclin-dependent kinase 1 (cdk-1), mbk-1/human dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A), daf-21/Hsp90, prefoldin 6 (pfd-6), suppressor of ACY-4 sterility 1 (sacy-1), lbp-3/fatty acid-binding protein, K02D7.1/purine nucleoside phosphorylase, kin-4/microtubule-associated serine/threonine kinase, and daf-18/phosphatase and tensin homolog (PTEN). Asterisk (*), new alleles.