C-elegans Eats Its Own Intestine to Make Yolk Leading to Multiple Senescent Pathologies

被引:112
作者
Ezcurra, Marina [1 ,2 ,3 ]
Benedetto, Alexandre [1 ,2 ,4 ]
Sornda, Thanet [1 ,2 ,5 ]
Gilliat, Ann F. [1 ,2 ]
Au, Catherine [1 ,2 ]
Zhang, Qifeng [6 ]
van Schelt, Sophie [1 ,2 ]
Petrache, Alexandra L. [1 ,2 ]
Wang, Hongyuan [1 ,2 ]
de la Guardia, Yila [1 ,2 ]
Bar-Nun, Shoshana [7 ]
Tyler, Eleanor [1 ,2 ]
Wakelam, Michael J. [6 ]
Gems, David [1 ,2 ]
机构
[1] UCL, Inst Hlth Ageing, Mortimer St, London WC1E 6BT, England
[2] UCL, Dept Genet Evolut & Environm, Mortimer St, London WC1E 6BT, England
[3] Queen Mary Univ London, Sch Biol & Chem Sci, London E1 4NS, England
[4] Univ Lancaster, Fac Hlth & Med, Div Biomed & Life Sci, Lancaster LA1 4YW, England
[5] Naresuan Univ, Fac Med Sci, Dept Biochem, Phitsanulok 65000, Thailand
[6] Babraham Inst, Babraham Res Campus, Cambridge CB22 3AT, England
[7] Tel Aviv Univ, George S Wise Fac Life Sci, Tel Aviv, Israel
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
CAENORHABDITIS-ELEGANS; LIFE-SPAN; PROTEIN-TURNOVER; AUTOPHAGY GENES; LONGEVITY; GENETICS; SLOWS; MUTATION; NEMATODE; PROGRAM;
D O I
10.1016/j.cub.2018.06.035
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Aging (senescence) is characterized by the development of numerous pathologies, some of which limit lifespan. Key to understanding aging is discovery of the mechanisms (etiologies) that cause senescent pathology. In C. elegans, a major senescent pathology of unknown etiology is atrophy of its principal metabolic organ, the intestine. Here we identify a cause of not only this pathology but also of yolky lipid accumulation and redistribution (a form of senescent obesity): autophagy-mediated conversion of intestinal biomass into yolk. Inhibiting intestinal autophagy or vitellogenesis rescues both visceral pathologies and can also extend lifespan. This defines a disease syndrome leading to multimorbidity and contributing to late-life mortality. Activation of gut-to-yolk biomass conversion by insulin/IGF-1 signaling (IIS) promotes reproduction and senescence. This illustrates how major, IIS-promoted senescent pathologies in C. elegans can originate not from damage accumulation but from direct effects of futile, continued action of a wild-type biological program (vitellogenesis).
引用
收藏
页码:2544 / +
页数:18
相关论文
共 61 条
[1]   The free radical theory of aging matures [J].
Beckman, KB ;
Ames, BN .
PHYSIOLOGICAL REVIEWS, 1998, 78 (02) :547-581
[2]   Aging and immortality - Quasi-programmed senescence and its pharmacologic inhibition [J].
Blagosklonny, Mikhail V. .
CELL CYCLE, 2006, 5 (18) :2087-2102
[3]   Revisiting the antagonistic pleiotropy theory of aging TOR-driven program and quasi-program [J].
Blagosklonny, Mikhail V. .
CELL CYCLE, 2010, 9 (16) :3151-3156
[4]  
BRENNER S, 1974, GENETICS, V77, P71
[5]   Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging [J].
Chang, Jessica T. ;
Kumsta, Caroline ;
Hellman, Andrew B. ;
Adams, Linnea M. ;
Hansen, Malene .
ELIFE, 2017, 6
[6]   Tissue-specific autophagy responses to aging and stress in C-elegans [J].
Chapin, Hannah C. ;
Okada, Megan ;
Merz, Alexey J. ;
Miller, Dana L. .
AGING-US, 2015, 7 (06) :419-434
[7]   Anthranilate Fluorescence Marks a Calcium-Propagated Necrotic Wave That Promotes Organismal Death in C. elegans [J].
Coburn, Cassandra ;
Allman, Erik ;
Mahanti, Parag ;
Benedetto, Alexandre ;
Cabreiro, Filipe ;
Pincus, Zachary ;
Matthijssens, Filip ;
Araiz, Caroline ;
Mandel, Abraham ;
Vlachos, Manolis ;
Edwards, Sally-Anne ;
Fischer, Grahame ;
Davidson, Alexander ;
Pryor, Rosina E. ;
Stevens, Ailsa ;
Slack, Frank J. ;
Tavernarakis, Nektarios ;
Braeckman, Bart P. ;
Schroeder, Frank C. ;
Nehrke, Keith ;
Gems, David .
PLOS BIOLOGY, 2013, 11 (07)
[8]   Autophagy: in sickness and in health [J].
Cuervo, AM .
TRENDS IN CELL BIOLOGY, 2004, 14 (02) :70-77
[9]   Run-on of germline apoptosis promotes gonad senescence in C. elegans [J].
de la Guardia, Yila ;
Gilliat, Ann F. ;
Hellberg, Josephine ;
Rennert, Peter ;
Cabreiro, Filipe ;
Gems, David .
ONCOTARGET, 2016, 7 (26) :39082-39096
[10]  
DePina Ana S., 2011, BMC Physiology, V11, P11, DOI 10.1186/1472-6793-11-11