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New genes that extend Caenorhabditis elegans' lifespan in response to reproductive signals.
Aging Cell. 2012 Apr; 11(2):192-202
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11 Feb 2012
New Finding
DOI: 10.3410/f.13689956.15103060
Ablation of the germline significantly extends lifespan in both Caenorhabditis elegans and Drosophila, but how signals from the reproductive system modulate aging still remains poorly understood. In the nematode, it has been previously found that the forkhead transcription factor DAF-16, downstream...Continue reading
Ablation of the germline significantly extends lifespan in both Caenorhabditis elegans and Drosophila, but how signals from the reproductive system modulate aging still remains poorly understood. In the nematode, it has been previously found that the forkhead transcription factor DAF-16, downstream of insulin signaling, and the steroid hormone receptor DAF-12 are part of the germline longevity pathway, but whether and how these two genes interact to regulate downstream target genes is unknown. In this paper, the Kenyon group has, for the first time, used microarray analysis to discover transcriptional targets of the germline longevity pathway regulated by DAF-16 and DAF-12.
The authors find that both transcription factors affect distinct but overlapping sets of target genes in response to germline ablation. Importantly, the study also uncovers several new genes not previously known to be functionally required for germline ablation to extend lifespan. Given the common - if not ubiquitous - trade-off between reproduction and lifespan in animals, these results advance our understanding of the molecular mechanisms underlying the regulation of lifespan by signals emanating from the gonads.
The authors find that both transcription factors affect distinct but overlapping sets of target genes in response to germline ablation. Importantly, the study also uncovers several new genes not previously known to be functionally required for germline ablation to extend lifespan. Given the common - if not ubiquitous - trade-off between reproduction and lifespan in animals, these results advance our understanding of the molecular mechanisms underlying the regulation of lifespan by signals emanating from the gonads.
Disclosures
None declared
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Flatt T: F1000Prime Recommendation of [McCormick M et al., Aging Cell 2012, 11(2):192-202]. In F1000Prime, 11 Feb 2012; DOI: 10.3410/f.13689956.15103060. F1000Prime.com/13689956#eval15103060
F1000Prime Recommendations, Dissents and Comments for [McCormick M et al., Aging Cell 2012, 11(2):192-202]. In F1000Prime, 19 May 2013; F1000Prime.com/13689956
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In Caenorhabditis elegans and Drosophila, removing germline stem cells increases lifespan. In C. elegans, this lifespan extension requires DAF-16, a FOXO transcription factor, and DAF-12, a nuclear hormone receptor. To better understand the regulatory relationships between DAF-16 and DAF-12, we used microarray analysis to identify downstream genes. We found that these two transcription factors influence the expression of distinct but overlapping sets of genes in response to loss of the germline. In addition, we identified several new genes that are required for loss of the germline to increase lifespan. One, phi-62, encodes a conserved, predicted RNA-binding protein. PHI-62 influences DAF-16-dependent transcription, possibly by collaborating with TCER-1, a putative transcription elongation factor, and FTT-2, a 14-3-3 protein known to bind DAF-16. Three other genes encode proteins involved in lipid metabolism; one is a triacylglycerol lipase, and another is an acyl-CoA reductase. These genes do not noticeably affect bulk fat storage levels; therefore, we propose a model in which they may influence production of a lifespan-extending signal or metabolite.
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
DOI: 10.1111/j.1474-9726.2011.00768.x
PMID: 22081913
