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daf-41/p23: A Small Protein Heating Up Lifespan Regulation.

Richter K - PLoS Genet. (2015)

View Article: PubMed Central - PubMed

Affiliation: Department Chemie, Technische Universität München, Garching, Germany; Center for Integrated Protein Science Munich CIPS, Munich, Germany.

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Nematodes, like Caenorhabditis elegans with their 20 days of adult life, have proven to be excellent model systems to study organismal lifespan, its variability, and its regulation... This is evident from a clear relationship between temperature and life span ranging from 35 days to 9 days upon temperature changes from 10 to 25.5 degrees... On the higher end of this temperature range, C. elegans can enter the dauer state, which is also found in response to starvation or the presence of dauer pheromone... The formation of this stress-resistant state, which enables survival of the organism for longer than 3 months, requires morphological changes to the cuticule and inhibition of further development... Interestingly, it is entirely reversible without effects on the later adult life span... Interestingly, several genes that control the entry into the stress- and starvation-resistant dauer state also exert control over the normal life span of the nematode... Early aging markers include disorganization of muscular structure and reduction of pharyngeal activity and motility... In this issue of PLOS Genetics, Horikawa and coworkers address critical questions at the crossroads of stress-resistance, longevity, and chaperone involvement by investigating a deletion mutant of the cochaperone p23, an effector protein of Hsp90... Also, temperature-sensitive neurons had been reported to influence the aging process, similar to the findings reported here... In general, these studies show that development does not necessarily has to be slow at low temperatures and fast at high temperatures, and, importantly, with daf-41 a regulator is uncovered that influences this program... Thus, p23 appears to balance the transcriptional responses of these three transcription factors relevant for dauer formation, longevity, and aging, and in this way enables control over these processes at different temperatures... Hsp90 is known to regulate transcriptional outputs by influencing the activity of dozens of transcription factors via their cellular stability. p23, likewise, has been shown to influence the activity of transcription factors, including steroid hormone receptors and HSF-1... With the study of Horikawa and coworkers, this chaperone machinery now also moves into the center of life span regulation... Previously Hsp90, like p23, was found to regulate Hsf1 activity, and its depletion strongly induces the heat-shock response... The present study thus integrates the cellular chaperone network surrounding the molecular chaperone Hsp90/DAF-21 into the complex decision making to enter the dauer state and to determine the organismal life span.

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Related in: MedlinePlus

Nematode lifespan is regulated by temperature amongst other influences.This temperature dependence is the result of transcriptional networks and DAF-41/p23, which influences the transcriptional activities of HSF-1, DAF-12, and DAF-16.
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pgen.1005188.g001: Nematode lifespan is regulated by temperature amongst other influences.This temperature dependence is the result of transcriptional networks and DAF-41/p23, which influences the transcriptional activities of HSF-1, DAF-12, and DAF-16.

Mentions: In this issue of PLOS Genetics, Horikawa and coworkers address critical questions at the crossroads of stress-resistance, longevity, and chaperone involvement by investigating a deletion mutant of the cochaperone p23, an effector protein of Hsp90. They first determine that the deletion strain constitutively enters dauer and name the gene daf-41. They find that the usual temperature-dependence of the lifespan is altered in this strain with a much smaller temperature-influence than known for the wild-type background (Fig 1). This makes the deletion strain short lived at low temperatures and long lived at high temperatures. While it has been thought up until recently that the slow development and aging at low temperatures reflects the slower turnover of metabolites and the slower rate of all biochemical processes based on plain physical principles, being able to influence this effect by genetic means implies the existence of a biological control. Recent reports had suggested that such programs may exist [21]. Also, temperature-sensitive neurons had been reported to influence the aging process, similar to the findings reported here [22]. In general, these studies show that development does not necessarily has to be slow at low temperatures and fast at high temperatures, and, importantly, with daf-41 a regulator is uncovered that influences this program.


daf-41/p23: A Small Protein Heating Up Lifespan Regulation.

Richter K - PLoS Genet. (2015)

Nematode lifespan is regulated by temperature amongst other influences.This temperature dependence is the result of transcriptional networks and DAF-41/p23, which influences the transcriptional activities of HSF-1, DAF-12, and DAF-16.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492944&req=5

pgen.1005188.g001: Nematode lifespan is regulated by temperature amongst other influences.This temperature dependence is the result of transcriptional networks and DAF-41/p23, which influences the transcriptional activities of HSF-1, DAF-12, and DAF-16.
Mentions: In this issue of PLOS Genetics, Horikawa and coworkers address critical questions at the crossroads of stress-resistance, longevity, and chaperone involvement by investigating a deletion mutant of the cochaperone p23, an effector protein of Hsp90. They first determine that the deletion strain constitutively enters dauer and name the gene daf-41. They find that the usual temperature-dependence of the lifespan is altered in this strain with a much smaller temperature-influence than known for the wild-type background (Fig 1). This makes the deletion strain short lived at low temperatures and long lived at high temperatures. While it has been thought up until recently that the slow development and aging at low temperatures reflects the slower turnover of metabolites and the slower rate of all biochemical processes based on plain physical principles, being able to influence this effect by genetic means implies the existence of a biological control. Recent reports had suggested that such programs may exist [21]. Also, temperature-sensitive neurons had been reported to influence the aging process, similar to the findings reported here [22]. In general, these studies show that development does not necessarily has to be slow at low temperatures and fast at high temperatures, and, importantly, with daf-41 a regulator is uncovered that influences this program.

View Article: PubMed Central - PubMed

Affiliation: Department Chemie, Technische Universität München, Garching, Germany; Center for Integrated Protein Science Munich CIPS, Munich, Germany.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Nematodes, like Caenorhabditis elegans with their 20 days of adult life, have proven to be excellent model systems to study organismal lifespan, its variability, and its regulation... This is evident from a clear relationship between temperature and life span ranging from 35 days to 9 days upon temperature changes from 10 to 25.5 degrees... On the higher end of this temperature range, C. elegans can enter the dauer state, which is also found in response to starvation or the presence of dauer pheromone... The formation of this stress-resistant state, which enables survival of the organism for longer than 3 months, requires morphological changes to the cuticule and inhibition of further development... Interestingly, it is entirely reversible without effects on the later adult life span... Interestingly, several genes that control the entry into the stress- and starvation-resistant dauer state also exert control over the normal life span of the nematode... Early aging markers include disorganization of muscular structure and reduction of pharyngeal activity and motility... In this issue of PLOS Genetics, Horikawa and coworkers address critical questions at the crossroads of stress-resistance, longevity, and chaperone involvement by investigating a deletion mutant of the cochaperone p23, an effector protein of Hsp90... Also, temperature-sensitive neurons had been reported to influence the aging process, similar to the findings reported here... In general, these studies show that development does not necessarily has to be slow at low temperatures and fast at high temperatures, and, importantly, with daf-41 a regulator is uncovered that influences this program... Thus, p23 appears to balance the transcriptional responses of these three transcription factors relevant for dauer formation, longevity, and aging, and in this way enables control over these processes at different temperatures... Hsp90 is known to regulate transcriptional outputs by influencing the activity of dozens of transcription factors via their cellular stability. p23, likewise, has been shown to influence the activity of transcription factors, including steroid hormone receptors and HSF-1... With the study of Horikawa and coworkers, this chaperone machinery now also moves into the center of life span regulation... Previously Hsp90, like p23, was found to regulate Hsf1 activity, and its depletion strongly induces the heat-shock response... The present study thus integrates the cellular chaperone network surrounding the molecular chaperone Hsp90/DAF-21 into the complex decision making to enter the dauer state and to determine the organismal life span.

No MeSH data available.


Related in: MedlinePlus