Synergism between soluble guanylate cyclase signaling and neuropeptides extends lifespan in the nematode<i>Caenorhabditis elegans</i>

Abergel, R. Patrick; Livshits, Leonid; Shaked, Maayan; Chatterjee, Arijit; Gross, Einav

doi:10.1111/acel.12569

Cited by 13 publications

(15 citation statements)

References 41 publications

(64 reference statements)

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“…It has been previously shown that both E. coli HT115 and OP50 differentially modulate the metabolism, behavior, development and aging of worms [ 53 ] up to an extent that certain genes may have opposite effects on the lifespan of worms fed on OP50 and HT115 [ 54 - 56 ]. Similarly, the use of UV-killed bacteria may differentially affect the lifespan of certain mutants [ 57 ]. Most of the previously published hif-1 (ia4) worm lifespan experiments have been performed on UV-killed OP50 [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

HIF-1–dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA–binding protein MAA-1

Shamalnasab

Dhaoui

Thondamal

et al. 2017

Aging

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In yeast, the broadly conserved acyl-CoA–binding protein (ACBP) is a negative regulator of stress resistance and longevity. Here, we have turned to the nematode C. elegans as a model organism in which to determine whether ACBPs play similar roles in multicellular organisms. We systematically inactivated each of the seven C. elegans ACBP paralogs and found that one of them, maa-1 (which encodes membrane-associated ACBP 1), is indeed involved in the regulation of longevity. In fact, loss of maa-1 promotes lifespan extension and resistance to different types of stress. Through genetic and gene expression studies we have demonstrated that HIF-1, a master transcriptional regulator of adaptation to hypoxia, plays a central role in orchestrating the anti-aging response induced by MAA-1 deficiency. This response relies on the activation of molecular chaperones known to contribute to maintenance of the proteome. Our work extends to C. elegans the role of ACBP in aging, implicates HIF-1 in the increase of lifespan of maa-1 –deficient worms, and sheds light on the anti-aging function of HIF-1. Given that both ACBP and HIF-1 are highly conserved, our results suggest the possible involvement of these proteins in the age-associated decline in proteostasis in mammals.

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Section: Discussionmentioning

confidence: 99%

HIF-1–dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA–binding protein MAA-1

Shamalnasab

Dhaoui

Thondamal

et al. 2017

Aging

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“…Unc-9 is expressed in glutamatergic sensory neurons that respond to chemical, temperature and oxygen cues which are known to influence lifespan. However, these neurons do so by regulating daf-16 FOXO signalling 51,54,83 . Our data show that unc-9 acts independently of daf-16 to regulate longevity, making it unlikely that unc-9 regulates lifespan in these neurons.…”

Section: Discussionmentioning

confidence: 99%

“…These neuron classes show intriguing shared features: they are dominated by sensory neurons -19 of the 31 classes are sensory neurons. Sensory perception plays a central role in regulating C. elegans lifespan 49,50 , and chemosensory 51 , thermosensory 52,53 and oxygensensing neurons 54,55 have been shown to shorten or extend the animals' lifespan in an environmental context-dependent manner. The oxygen-sensing neurons AQR and PQR signal tonically at 21% ambient oxygen but are largely inactive at reduced O2 levels (7%) 56 .…”

Section: The Glutamatergic Unc-9-expressing Neurons Are Predominantlymentioning

confidence: 99%

Gap junctions in theC. elegansnervous system regulate ageing and lifespan

Vladis

Fischer

Digalaki

et al. 2019

Preprint

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The nervous system is a central regulator of longevity, but how neuronal communication interfaces with ageing pathways is not well understood. Gap junctions are key conduits that allow voltage and metabolic signal transmission across cellular networks, yet it has remained unexplored whether they play a role in regulating ageing and longevity. We show that the innexin genes encoding gap junction subunits in Caenorhabditis elegans have extensive and diverse impacts on lifespan. Loss of the neural innexin unc-9 increases longevity by a third and also strongly benefits healthspan. Unc-9 acts specifically in a glutamatergic circuit linked to mechanosensation. Absence of unc-9 depends on a functional touch-sensing machinery to regulate lifespan and alters the age-dependent decline of mechanosensory neurons. The life extension produced by removal of unc-9 requires reactive oxygen species. Our work reveals for the first time that gap junctions are important regulators of ageing and lifespan.is currently unknown whether gap junction coupling as a key intercellular communication channel contributes to the regulation of ageing and longevity.Here we set out to explore if gap junctions affect ageing using the nematode Caenorhabditis elegans, an outstanding model for studies on ageing 14,15 . We assayed the lifespan of loss-offunction mutants of most of the 25 C. elegans innexins and discovered that innexins have a significant impact on lifespan, some leading to an extension of lifespan while others shorten it. Surprisingly, most null mutations of neural innexins extended lifespan, with loss of unc-9, the most widely expressed innexin in the nervous system, increasing longevity by a third. Its selective removal from glutamatergic neurons led to an increase in lifespan and points to a mechanosensory circuit where UNC-9 regulates ageing. Our results show that UNC-9 alters the age-dependent decline of touch-sensing neurons and depends on functional touch sensation as well as reactive oxygen species to modulate lifespan. This study gives strong evidence to suggest an important and previously unknown role for gap junction intercellular communication in shaping ageing and longevity. ResultsThe C. elegans gap junction genes regulate longevity As there is extensive intercellular gap junction coupling in all organs of C. elegans, we hypothesised that gap junction channels may play specific roles in organismal ageing and longevity. The channel subunits encoded by 25 innexin genes show diverse, highly combinatorial, plastic and dynamic expression in virtually all organs and cells of this animal.The gap junction channels these innexins form play key roles in intercellular communication [16][17][18] . We asked if innexins influence longevity, which has not been known. To this end we performed lifespan assays in loss-of-function mutants of all innexins except inx-3, inx-12 and inx-13; these genes are essential for embryonic development or osmoregulation and their loss confers a lethal phenotype 18,19 . Loss-of-function mutants are availab...

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“…The lifespan of npr-1(−) worms was slightly, but significantly, longer than that of N2 animals bearing the npr-1(215V) allele [ 4 ]. This result fitted our prediction that the aggregation behaviour can create a “healthier O 2 microenvironment” and thus increases the lifespan of npr-1(−) worms.…”

mentioning

confidence: 99%

“…However, the result was the opposite. The lifespan of gcy-35(−);npr-1(−) worms was profoundly longer than that of both N2 and npr-1(−) worms [ 4 ]. In fact, the joint effect of gcy-35(−) and npr-1(−) on worm lifespan is synergistic, since gcy-35(−) worm lifespan was similar to N2 and npr-1(−) by itself elicits only a small increase in lifespan.…”

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confidence: 99%