Phenotypic Covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

Amrit, Francis Raj Gandhi; Boehnisch, Claudia; May, Robin C.

doi:10.1371/journal.pone.0009978

Cited by 35 publications

(30 citation statements)

References 55 publications

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“…Indeed, a recent study indicates that genes involved in lifespan regulation also contribute to stress resistance and robustness [18]. In our experiment, condition-dependent mortality selected for individuals that are better at resisting increased ambient temperature [19], a trait that has been shown to be associated with whole-organism performance and longevity [16]. Therefore, the proportion of robust individuals should increase over time in the course of evolution under condition-dependent mortality.…”

Section: Discussionmentioning

confidence: 89%

Why ageing stops: heterogeneity explains late-life mortality deceleration in nematodes

2013

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While ageing is commonly associated with exponential increase in mortality with age, mortality rates paradoxically decelerate late in life resulting in distinct mortality plateaus. Late-life mortality plateaus have been discovered in a broad variety of taxa, including humans, but their origin is hotly debated. One hypothesis argues that deceleration occurs because the individual probability of death stops increasing at very old ages, predicting the evolution of earlier onset of mortality plateaus under increased rate of extrinsic mortality. By contrast, heterogeneity theory suggests that mortality deceleration arises from individual differences in intrinsic lifelong robustness and predicts that variation in robustness between populations will result in differences in mortality deceleration. We used experimental evolution to directly test these predictions by independently manipulating extrinsic mortality rate (high or low) and mortality source (random death or condition-dependent) to create replicate populations of nematodes, Caenorhabditis remanei that differ in the strength of selection in late-life and in the level of lifelong robustness. Latelife mortality deceleration evolved in response to differences in mortality source when mortality rate was held constant, while there was no consistent response to differences in mortality rate. These results provide direct experimental support for the heterogeneity theory of late-life mortality deceleration.

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Section: Discussionmentioning

confidence: 89%

Why ageing stops: heterogeneity explains late-life mortality deceleration in nematodes

2013

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“…DAF-2 is the C. elegans insulin receptor (InR) homologue and it functions as a suppressor of daf-16 36, 52 . daf-2 ( e1370 ) mutation led to constitutively active daf-16 signaling 53 . Unlike WT animals (Fig.…”

Section: Resultsmentioning

confidence: 99%

Age- and manganese-dependent modulation of dopaminergic phenotypes in a C. elegans DJ-1 genetic model of Parkinson's disease

et al. 2015

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Parkinson’s Disease (PD) is the second most common neurodegenerative disease, yet its etiology and pathogenesis are poorly understood. PD is characterized by selective dopaminergic (DAergic) degeneration and progressive hypokinetic motor impairment. Mutations in dj-1 cause autosomal recessive early-onset PD. DJ-1 is thought to protect DAergic neurons via an antioxidant mechanism, but the precise basis of this protection has not yet been resolved. Aging and manganese (Mn) exposure are significant non-genetic risk factors for PD. Caenorhabditis elegans (C. elegans) is an optimal model for PD and aging studies because of its simple nervous system, conserved DAergic machinery, and short 20-day lifespan. Here we tested the hypothesis that C. elegans DJ-1 homologues were protective against Mn-induced DAergic toxicity in an age-dependent manner. We showed that the deletion of C. elegans DJ-1 related (djr) genes, djr-1.2, decreased survival after Mn exposure. djr-1.2, the DJ-1 homologue was expressed in DAergic neurons and its deletion decreased lifespan and dopamine (DA)-dependent dauer movement behavior after Mn exposure. We also tested the role of DAF-16 as a regulator of dj-1.2 interaction with Mn toxicity. Lifespan defects resulting from djr-1.2 deletion could be restored to normal by overexpression of either DJR-1.2 or DAF-16. Furthermore, dauer movement alterations after djr-1.2 deletion were abolished by constitutive activation of DAF-16 through mutation of its inhibitor, DAF-2 insulin receptor. Taken together, our results reveal PD-relevant interactions between aging, the PD environmental risk factor manganese, and homologues of the established PD genetic risk factor DJ-1. Our data demonstrate a novel role for the DJ-1 homologue, djr-1.2, in mitigating Mn-dependent lifespan reduction and DA signaling alterations, involving DAF-2/DAF-16 signaling.

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“…Resistance to stress is one of the important determinants of animal survival and longevity (Jazwinski, 1998). Indeed, within a wide variety of species, individuals or strains with longer life spans generally demonstrate a higher resistance to environmental and/or physiological stress and vice versa (Sohal et al, 1990; Lithgow et al, 1995; Murakami and Johnson, 1996; Lin et al, 1998; Guarente and Kenyon, 2000; Fabrizio et al, 2001; Landis et al, 2003; Brown-Borg, 2006; Masse et al, 2008; Ungvari et al, 2008; Labinskyy et al, 2009; Perez et al, 2009; Amrit et al, 2010; Slack et al, 2010). For example, selection for stress resistance in Drosophila increases its life span (Rose et al, 1992; Harshman et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Gadd45 proteins: Relevance to aging, longevity and age-related pathologies

Moskalev

Smit-McBride

Shaposhnikov

et al. 2012

Ageing Research Reviews

127

124

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The Gadd45 proteins have been intensively studied, in view of their important role in key cellular processes. Indeed, the Gadd45 proteins stand at the crossroad of the cell fates by controlling the balance between cell (DNA) repair, eliminating (apoptosis) or preventing the expansion of potentially dangerous cells (cell cycle arrest, cellular senescence), and maintaining the stem cell pool. However, the biogerontological aspects have not thus far received sufficient attention. Here we analyzed the pathways and modes of action by which Gadd45 members are involved in aging, longevity and age-related diseases. Because of their pleiotropic action, a decreased inducibility of Gadd45 members may have far-reaching consequences including genome instability, accumulation of DNA damage, and disorders in cellular homeostasis – all of which may eventually contribute to the aging process and age-related disorders (promotion of tumorigenesis, immune disorders, insulin resistance and reduced responsiveness to stress). Most recently, the dGadd45 gene has been identified as a longevity regulator in Drosophila. Although further wide-scale research is warranted, it is becoming increasingly clear that Gadd45s are highly relevant to aging, age-related diseases (ARDs) and to the control of life span, suggesting them as potential therapeutic targets in ARDs and pro-longevity interventions.

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Phenotypic Covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

Cited by 35 publications

References 55 publications

Why ageing stops: heterogeneity explains late-life mortality deceleration in nematodes

Why ageing stops: heterogeneity explains late-life mortality deceleration in nematodes

Age- and manganese-dependent modulation of dopaminergic phenotypes in a C. elegans DJ-1 genetic model of Parkinson's disease

Gadd45 proteins: Relevance to aging, longevity and age-related pathologies

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