A parthenogenetic quasi-program causes teratoma-like tumors during aging in wild-type C. elegans

Wang, Hongyuan and Zhao, Yuan and Ezcurra, Marina and Benedetto, Alexandre and Gilliat, Ann F. and Hellberg, Josephine and Ren, Ziyu and Galimov, Evgeniy R. and Athigapanich, Trin and Girstmair, Johannes and Telford, Maximilian J. and Dolphin, Colin T. and Zhang, Zhizhou and Gems, David (2018) A parthenogenetic quasi-program causes teratoma-like tumors during aging in wild-type C. elegans. npj Aging and Mechanisms of Disease, 4 (1): 6. ISSN 2056-3973

Abstract

Many diseases whose frequency increases with advancing age are caused by aging (senescence), but the mechanisms of senescence remain poorly understood. According to G.C. Williams and M.V. Blagosklonny, a major etiological determinant of senescence is late-life, wild-type gene action and non-adaptive execution of biological programs (or quasi-programs). These generate a wide range of senescent pathologies causing illness and death. Here we investigate the etiology of a prominent senescent pathology in the nematode C. elegans, uterine tumors, in the light of the Williams Blagosklonny theory. Uterine tumors develop from unfertilized, immature oocytes which execute incomplete embryogenetic programs. This includes extensive endomitosis, leading to formation of chromatin masses and cellular hypertrophy. The starting point of pathogenesis is exhaustion of sperm stocks. The timing of this transition between program and quasi-program can be altered by blocking sperm production (causing earlier tumors) or supplying additional sperm by mating (delaying tumor onset). Other pathophysiological determinants are yolk consumption by tumors, and bacterial proliferation within tumors. Uterine tumors resemble mammalian ovarian teratomas (tera, Greek: monster) in that both develop from oocytes that fail to mature after meiosis I, and both are the result of quasi-programs. Moreover, older but not younger uterine tumors show expression of markers of later embryogenesis, i.e. are teratoma-like. These results show how uterine tumors in C. elegans form as the result of run-on of embryogenetic quasi-programs. They also suggest fundamental etiological equivalence between teratoma and some forms of senescent pathology, insofar as both are caused by quasi-programs.