The role of insulin/IGF-1 signaling in the longevity of model invertebrates, C. elegans and D. melanogaster

Abstract

Insulin/insulin-like growth factor (IGF)-1 signaling (IIS) pathway regulates aging in many organisms, ranging from simple invertebrates to mammals, including humans. Many seminal discoveries regarding the roles of IIS in aging and longevity have been made by using the roundworm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. In this review, we describe the mechanisms by which various IIS components regulate aging in C. elegans and D. melanogaster. We also cover systemic and tissue-specific effects of the IIS components on the regulation of lifespan. We further discuss IIS-mediated physiological processes other than aging and their effects on human disease models focusing on C. elegans studies. As both C. elegans and D. melanogaster have been essential for key findings regarding the effects of IIS on organismal aging in general, these invertebrate models will continue to serve as workhorses to help our understanding of mammalian aging. [BMB Reports 2016; 49(2): 81-92]

Identification of miR‐305, a microRNA that promotes aging, and its target mRNAs in Drosophila

“…The IIS pathway is highly conserved among multicellular organisms and plays an important role in energy production through the stimulation of sugar uptake (Barbieri, Bonafè, Franceschi, & Paolisso, ; Taleman, ). It has been reported that the inhibition of these pathways results in lifespan extension (Altintas, Park, & Lee, ; Barbieri et al., ; Clancy et al., ; Friedman & Johnson, ; Holzenberger et al., ; Tatar et al., ). Our RNA‐seq analysis showed that the tobi mRNA, a target gene for insulin in the brain, and mRNAs for the insulin‐like peptides dilp2 and dilp5 increased upon miR‐305 over‐expression.…”

“…Thus, we speculate that miR‐305 targets and negatively regulates the dilp6 mRNA, which results in the increased expression of dilp2 . It has been reported that a reduction in the sugar metabolism eventually leads to an extension of lifespan in Drosophila (Altintas et al., ; Huang et al., ). Another report also showed that the ectopic expression of Foxo, which is negatively regulated by the IIS signaling pathway, resulted in lifespan extension (Demontis & Perrimon, ).…”

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging

“…elegans is also an established model organism for the study of aging [20–22]. Work in multiple systems has demonstrated that aging is a highly regulated process that is under tight genetic control [23–25]. A hallmark of aging is the decreased ability to maintain protein function or protein homeostasis (proteostasis), which results in increased cellular damage and decline of cellular and organismal functions [26–29].…”

Linking the why and how of aging; evidence for somatotropic control of long-term memory function in the pond snail Lymnaea stagnalis

“…Likewise, the idea of ILP involvement in the regulation of aspects of ageing is, by itself, not a novel one (Sadagurski and White, 2013;Altintas et al, 2016). Yet, the present study adds to what we see as a fascinating novel perspective to this field: by associating the LLs, two tiny accessory CNS lobes that arguably constitute a metabolic control centre in L. stagnalis, with the associative learning abilities of an animal, we have may have identified the embodiment of a nexus of ultimate evolutionary causes of ageing and proximate mechanisms of brain ageing in this model system.…”