Chaperoning extended life

Tatar, Marc; Khazaeli, Aziz A.; Curtsinger, James W.

doi:10.1038/36237

Cited by 313 publications

(176 citation statements)

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“…Glutathione S-transferase and cytochrome P450 are involved in detoxification, one of the determinants of aging (1,34). Heat shock proteins enhance resistance to stress and extend lifespan (35,36). All of these genes were induced by PBA, as confirmed in Fig.…”

Section: Resultssupporting

confidence: 50%

Life extension in Drosophila by feeding a drug

Kang

Benzer

Min

2002

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

284

176

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We report that feeding Drosophila throughout adulthood with 4-phenylbutyrate (PBA) can significantly increase lifespan, without diminution of locomotor vigor, resistance to stress, or reproductive ability. Treatment for a limited period, either early or late in adult life, is also effective. Flies fed PBA show a global increase in histone acetylation as well as a dramatically altered pattern of gene expression, including induction or repression of numerous genes. The delay in aging may result from the altered physiological state.

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Section: Resultssupporting

confidence: 50%

Life extension in Drosophila by feeding a drug

Kang

Benzer

Min

2002

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

284

176

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“…In Drosophila, increased copies of hsps and their overexpression are reported to have beneficial effect on the organism. Increased copy number of hsp70 has been reported to reduce mortality and improve overall survival of organism (Tatar et al 1997). Overexpression of hsp27 (Liao et al 2008) and hsp22 (Kim et al 2010) were shown to provide increased longevity to flies.…”

Section: Discussionmentioning

confidence: 99%

“…Genome-wide studies on age-associated gene expression changes in flies have shown the upregulation of heat shock genes (hsps) (Curtis et al 2007;Landis et al 2012). In addition, modulated expression of hsps (hsp70, hsp27, and hsp22) has been reported to alter life span in flies (Kim et al 2010;Liao et al 2008;Tatar et al 1997) and higher level of HSPs is reported in longerlived mammals and birds (Salway et al 2011). In the same context, improved health-and life span were observed in DCA-exposed Caenorhabditis elegans (Schaffer et al 2011).…”

mentioning

confidence: 99%

Long-term dietary exposure to low concentration of dichloroacetic acid promoted longevity and attenuated cellular and functional declines in aged Drosophila melanogaster

Pandey

Vimal

Chandra

et al. 2014

AGE

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Dichloroacetic acid (DCA), a water disinfection by-product, has attained emphasis due to its prospect for clinical use against different diseases including cancer along with negative impact on organisms. However, these reports are based on the toxicological as well clinical data using comparatively higher concentrations of DCA without much of environmental relevance. Here, we evaluate cellular as well as organismal effects of DCA at environmentally and mild clinically relevant concentrations (0.02-20.0 μg/ml) using an established model organism, Drosophila melanogaster. Flies were fed on food mixed with test concentrations of DCA for 12-48 h to examine the induction of reactive oxygen species (ROS) generation, oxidative stress (OS), heat shock genes (hsps) and cell death along with organismal responses. We also examined locomotor performance, ROS generation, glutathione (GSH) depletion, expression of GSH-synthesizing genes (gclc and gclm), and hsps at different days (0, 10, 20, 30, 40, 50) of the age in flies after prolonged DCA exposure. We observed mild OS and induction of antioxidant defense system in 20.0 μg/ml DCA-exposed organism after 24 h. After prolonged exposure to DCA, exposed organism exhibited improved survival, elevated expression of hsp27, gclc, and gclm concomitant with lower ROS generation and GSH depletion and improved locomotor performance. Conversely, hsp27 knockdown flies exhibited reversal of the above end points. The study provides evidence for the attenuation of cellular and functional decline in aged Drosophila after prolonged DCA exposure and the effect of hsp27 modulation which further incites studies towards the therapeutic application of DCA.

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“…14 A screen for genes that show differences in gene expression between normal and stress conditions identified several loci that had already been shown to affect lifespan, as well as two additional candidates, heat-shock protein (hsp) genes hsp26 and hsp27; independent overexpression of both genes extends lifespan. 15 Tests on other molecular chaperones that are induced in response to stress have shown that increasing copy numbers of hsp70 reduces the mortality rate after a non-lethal induction of stress, 16 and that overexpression of hsp22, either ubiquitously or in motor neurons, also extends lifespan. 17 Similarly, an extra copy of meiotic-41 (mei-41), which may repair DNA damaged by oxidative stress, increases longevity.…”

Section: Identification Of Aging Genesmentioning

confidence: 99%

Dissecting the genetics of longevity inDrosophila melanogaster

Paaby

Schmidt²

2009

Fly

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Drosophila melanogaster has been an historically important system for investigating the genetic basis of longevity, and will continue to be valuable as new technologies permit genomic explorations into the biology of aging. The utility of D. melanogaster resides in two resources: its powerful genetic tools as a model system, and a natural ecology that provides substantial genetic variation across significant environmental heterogeneity. Here we provide a review of the genetics of longevity in D. melanogaster, in which we describe the characterization of individual aging genes, the complexity of the genetic architecture of this quantitative trait, and the evaluation of natural genetic variation in the evolution of life histories.

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Chaperoning extended life

Cited by 313 publications

References 1 publication

Life extension in Drosophila by feeding a drug

Life extension in Drosophila by feeding a drug

Long-term dietary exposure to low concentration of dichloroacetic acid promoted longevity and attenuated cellular and functional declines in aged Drosophila melanogaster

Dissecting the genetics of longevity inDrosophila melanogaster

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