Evidence for only two independent pathways for decreasing senescence in Caenorhabditis elegans

Yen, Kelvin; Mobbs, Charles V.

doi:10.1007/s11357-009-9110-7

Cited by 24 publications

(38 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apart from the IIS pathway, the mitochondrial genes (clk-1) (Lakowski and Hekimi 1996) and dietary restriction genes (eat-2) (Yen and Mobbs 2010) are known to play a role in the aging process. In C. elegans, mutation in clk-1 gene causes extension of adult lifespan (Hekimi et al 1998).…”

Section: Discussionmentioning

confidence: 99%

“…In the case of 2 h exposed worms, the expression was meager as compared to control. b Quantification of the expressed HSF-1 was done using the ImageLab software many mammalian systems (Yen and Mobbs 2010). When exposed to UV-A, the level of expression of clk-1 was found to be decreasing and that of eat-2 was almost constant during the course of exposure in wild type worms.…”

Section: Discussionmentioning

confidence: 99%

“…UV-A-mediated aging is independent of mitochondrial signaling and dietary restriction Apart from the IIS pathway, the aging process is mediated by mitochondrial signaling (Lakowski and Hekimi 1996) and calorie restriction process (Yen and Mobbs 2010). Quantitative PCR analysis of clk-1 and eat-2 which are the key regulators of these above events were performed to confirm whether the aging process initiated by UV-A is dependent on any of these pathways.…”

Section: Uv-a Induces Damage In the Nematodementioning

confidence: 99%

See 2 more Smart Citations

Ultraviolet-A triggers photoaging in model nematode Caenorhabditis elegans in a DAF-16 dependent pathway

Prasanth

Santoshram

Bhaskar

et al. 2016

AGE

View full text Add to dashboard Cite

Ultraviolet radiations (UV) are the primary causative agent for skin aging (photoaging) and cancer, especially UV-A. The mode of action and the molecular mechanism behind the damages caused by UV-A is not well studied, in vivo. The current study was employed to investigate the impact of UV-A exposure using the model organism, Caenorhabditis elegans. Analysis of lifespan, healthspan, and other cognitive behaviors were done which was supported by the molecular mechanism.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Uv-a Induces Damage In the Nematodementioning

confidence: 99%

See 1 more Smart Citation

Ultraviolet-A triggers photoaging in model nematode Caenorhabditis elegans in a DAF-16 dependent pathway

Prasanth

Santoshram

Bhaskar

et al. 2016

AGE

View full text Add to dashboard Cite

show abstract

“…One approach is to assess physiological phenotypes that are known to deteriorate with age, such as cognition or the functioning of the cardiovascular or immune systems, to detect similarities or discrepancies with the patterns observed in control strains. An alternative criterion is to consider whether a particular manipulation changes how mortality rates increase with age (Sacher 1977;De Magalhaes et al 2005;Yen and Mobbs 2010). This is based on the hypothesis that the increased incidence of the age-related pathological changes that characterize the aging process is reflected in changing mortality rates.…”

mentioning

confidence: 99%

Different Mechanisms of Longevity in Long-Lived Mouse and Caenorhabditis elegans Mutants Revealed by Statistical Analysis of Mortality Rates

Hughes¹,

Hekimi

2016

Genetics

View full text Add to dashboard Cite

Mouse and Caenorhabditis elegans mutants with altered life spans are being used to investigate the aging process and how genes determine life span. The survival of a population can be modeled by the Gompertz function, which comprises two parameters. One of these parameters ("G") describes the rate at which mortality accelerates with age and is often described as the "rate of aging." The other parameter ("A") may correspond to the organism's baseline vulnerability to deleterious effects of disease and the environment. We show that, in mice, life-span-extending mutations systematically fail to affect the age-dependent acceleration of mortality (G), but instead affect only baseline vulnerability (A). This remains true even when comparing strains maintained under identical environmental conditions. In contrast, life-span-extending mutations in C. elegans were associated with decreases in G. These observations on mortality rate kinetics suggest that the mechanisms of aging in mammals might fundamentally differ from those in nematodes.KEYWORDS aging; Caenorhabditis elegans; Gompertz; longevity; mice T HE aging process can be studied by investigating genetic variants that alter life span in model organisms (Finch and Ruvkun 2001;Hekimi 2006). For example, the fact that mutations of genes involved in the insulin/insulin-like signaling pathway can extend life span in Caenorhabditis elegans, Drosophila, and mice is considered to imply a role for this pathway in the aging process (Kenyon 2010). Likewise, a role for mitochondrial function in aging is suggested by the finding that impairments to mitochondrial function can extend lifespan in C. elegans and mice (Ewbank et al. 1997;Dillin et al. 2002;Lee et al. 2003;Liu et al. 2005;Hughes and Hekimi 2011;Wang and Hekimi 2015).Another point of view is provided by the study of mutations in a number of genes that induce segmental progeroid syndromes and shorten life span in mice. The short life span of these mutant mice is accompanied by the accelerated expression of some of the phenotypes commonly encountered in aging . While these have often been presented as representing alterations to the aging process, it remains possible that their shorter life spans are caused by the induction of specific pathologies that only mimic aspects of the actual aging process (Harrison 1994;Miller 2004).It has also been argued that an extension of life span may not necessarily be concrete evidence of a retardation of the aging process (Orr et al. 2003;De Magalhaes et al. 2005;Ladiges et al. 2009). In this view, a life-span-extending intervention may simply remedy deficiencies in the environment or in the genetic makeup of one particular strain. The intervention would therefore extend life span by correcting specific flaws rather than altering the aging process. These considerations create a conundrum: If life span is not a reliable measure of aging, how can we confirm that a particular manipulation truly affects the aging process? One approach is to assess physiological phenotypes that ar...

show abstract

“…5A). Temperature has long been known to be a powerful decelerator of mortality rate (12,13,42) (Fig. 5B).…”

Section: Significancementioning

confidence: 99%

The 4E-BP growth pathway regulates the effect of ambient temperature on Drosophila metabolism and lifespan

Carvalho

Drago

Hoxha

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Changes in body temperature can profoundly affect survival. The dramatic longevity-enhancing effect of cold has long been known in organisms ranging from invertebrates to mammals, yet the underlying mechanisms have only recently begun to be uncovered. In the nematode Caenorhabditis elegans, this process is regulated by a thermosensitive membrane TRP channel and the DAF-16/FOXO transcription factor, but in more complex organisms the underpinnings of cold-induced longevity remain largely mysterious. We report that, in Drosophila melanogaster, variation in ambient temperature triggers metabolic changes in protein translation, mitochondrial protein synthesis, and posttranslational regulation of the translation repressor, 4E-BP (eukaryotic translation initiation factor 4E-binding protein). We show that 4E-BP determines Drosophila lifespan in the context of temperature changes, revealing a genetic mechanism for cold-induced longevity in this model organism. Our results suggest that the 4E-BP pathway, chiefly thought of as a nutrient sensor, may represent a master metabolic switch responding to diverse environmental factors.S tudies on the biological underpinnings of aging have uncovered numerous genetic and environmental factors regulating animal lifespan. Longevity-promoting genes include components of the insulin-like signaling pathway, the histone deacetylase Sir2, the GTPase Ras, TRP membrane channels, and transcription factors, among many others (1, 2). Environmental manipulations extending life include changes in nutrition (often referred to as caloric or dietary restriction), sexual/reproductive history, and ambient temperature (3-5).Of the factors known to impact aging, temperature is arguably the most promising. Lifespan extension by cold is evolutionarily conserved-documented in poikilotherms, such as worms and flies, and homeotherms, including mammals (4, 6-11)-and more robust than well-studied interventions such as dietary restriction (12, 13). However, the underlying mechanisms remain incompletely understood (10,14,15). In Caenorhabditis elegans, the effect of cold on survival involves the thermosensitive membrane channel TRPA-1 acting upstream of the DAF-16/FOXO transcription factor (14,15). This seminal finding countered the notion that longevity is the passive result of general thermodynamic changes, and favored instead the view that genetic pathways actively control lifespan in response to ambient temperature. However, these results have to date not been extended or replicated in other model organisms. Explanatory theories for the effect of cold on longevity include a reduction in reactive oxygen species generated by mitochondrial uncoupling proteins, suppression of autoimmune response, and changes in neuroendocrine factors (6,16,17), but these views remain largely speculative given the lack of further mechanistic insight into lifespan extension by cold in model organisms.We report that, in Drosophila, changes in temperature trigger a metabolic program impacting protein translation, mitochondrial prot...

show abstract

Evidence for only two independent pathways for decreasing senescence in Caenorhabditis elegans

Cited by 24 publications

References 74 publications

Ultraviolet-A triggers photoaging in model nematode Caenorhabditis elegans in a DAF-16 dependent pathway

Ultraviolet-A triggers photoaging in model nematode Caenorhabditis elegans in a DAF-16 dependent pathway

Different Mechanisms of Longevity in Long-Lived Mouse and Caenorhabditis elegans Mutants Revealed by Statistical Analysis of Mortality Rates

The 4E-BP growth pathway regulates the effect of ambient temperature on Drosophila metabolism and lifespan

Contact Info

Product

Resources

About