Fat metabolism links germline stem cells and longevity in C. elegans.
Fat metabolism, reproduction, and aging are intertwined regulatory axes; however, the mechanism by which they are coupled remains poorly understood. We found that germline stem cells (GSCs) actively modulate lipid hydrolysis in Caenorhabditis elegans, which in turn regulates longevity. GSC arrest promotes systemic lipolysis via induction of a specific fat lipase. Subsequently, fat mobilization is promoted and life span is prolonged. Constitutive expression of this lipase in fat storage tissue generates lean and long-lived animals. This lipase is a key factor in the lipid hydrolysis and increased longevity that are induced by decreased insulin signaling. These results suggest a link between C. elegans fat metabolism and longevity.
Wang
Meng C
MC
Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
O'Rourke
Eyleen J
EJ
Ruvkun
Gary
G
D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors; D017238:Genes, Helminth; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D006868:Hydrolysis; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D008136:Longevity; D023421:Models, Animal; D011972:Receptor, Insulin / Q000378:metabolism; D012098:Reproduction; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013696:Temperature; D014157:Transcription Factors / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; C517777:KRI-1 protein, C elegans; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D008049:Lipase