Regulation of longevity by the reproductive system

• Published in: Experimental gerontology Vol. 48; no. 7; pp. 596 - 602
• Main Author: Antebi, Adam
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.07.2013
• Subjects: Age Factors; Aging; Aging - genetics; Aging - metabolism; Aging - physiology; Animals; Autophagy; Cell Proliferation; Cellular Senescence; Energy Metabolism; Fat metabolism; Gene Expression Regulation; Gonad; Gonadal Steroid Hormones - metabolism; Gonads - metabolism; Gonads - physiology; Homeostasis; Hormone; Humans; Longevity; Models, Biological; Reproduction - genetics; Signal Transduction; Steroid; Transcription Factors - metabolism; Hormone; Steroid; IIS; Fat metabolism; Gonad; Aging; NHR; DA
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2012.09.009

Pioneering work in model organisms reveals that the reproductive system is involved not only in propagation of the species but also regulates organismal metabolism and longevity. In C. elegans, prevention of germline stem cell proliferation results in a 60% extension of lifespan, termed gonadal longevity. Gonadal longevity relies on the transcriptional activities of steroid nuclear receptor DAF-12, the FOXO transcription factor homolog DAF-16, the FOXA transcription factor homolog PHA-4, and the HNF-4-like nuclear receptor NHR-80. These transcription factors work in an integrated transcriptional network to regulate fatty acid lipolysis, autophagy, stress resistance and other processes, which altogether enhance homeostasis and extend life. Because the reproductive system also regulates longevity in other species, studies in C. elegans may shed light on ancient mechanisms governing reproduction and survival. ► Removal of germline stem cells extends C. elegans life span. ► Germline removal stimulates the transcriptional activities of FXR, FOXO, FOXA, and HNF4-alpha homologs. ► Transcriptional cascades regulate fatty acid desaturation, lipolysis, and autophagy to impact the life span.