Date Published: February 28, 2018
Publisher: John Wiley and Sons Inc.
Author(s): Stijn Mouton, Magda Grudniewska, Lisa Glazenburg, Victor Guryev, Eugene Berezikov.
Animals show a large variability of lifespan, ranging from short‐lived as Caenorhabditis elegans to immortal as Hydra. A fascinating case is flatworms, in which reversal of aging by regeneration is proposed, yet conclusive evidence for this rejuvenation‐by‐regeneration hypothesis is lacking. We tested this hypothesis by inducing regeneration in the sexual free‐living flatworm Macrostomum lignano. We studied survival, fertility, morphology, and gene expression as a function of age. Here, we report that after regeneration, genes expressed in the germline are upregulated at all ages, but no signs of rejuvenation are observed. Instead, the animal appears to be substantially longer lived than previously appreciated, and genes expressed in stem cells are upregulated with age, while germline genes are downregulated. Remarkably, several genes with known beneficial effects on lifespan when overexpressed in mice and C. elegans are naturally upregulated with age in M. lignano, suggesting that molecular mechanism for offsetting negative consequences of aging has evolved in this animal. We therefore propose that M. lignano represents a novel powerful model for molecular studies of aging attenuation, and the identified aging gene expression patterns provide a valuable resource for further exploration of anti‐aging strategies.
During the last decade, the large diversity of age‐related changes and life trajectories of different animals became increasingly clear (Jones et al., 2014). Studying species with aging profiles different from those of the established aging models, such as Caenorhabditis elegans, Drosophila melanogaster, and mice, offers insight into naturally occurring mechanisms to delay or suppress senescence and age‐related phenotypes. Particularly interesting are the few animals which are claimed to be immortal, such as Hydra, for which compelling evidence of a nonsenescent life trajectory exists (Martínez, 1998; Schaible et al., 2015) and certain flatworms (Haranghy & Balázs, 1964; Lange, 1968; Tan et al., 2012).
We showed that the flatworm rejuvenation theory is not valid in the sexual species M. lignano. However, all data taken together reveal that the regulation of fundamentally conserved mechanisms of cellular and organismal health maintenance evolved in M. lignano to efficiently offset negative consequences of aging. Therefore, we advocate that M. lignano is a novel powerful model toward studies of aging‐related genetic pathways, and we provide temporal gene expression patterns of aging in M. lignano as a resource to tap the power of this model.
MG, SM, VG, and EB conceptualized and designed the study; acquired, analyzed, and interpreted the data; and drafted the manuscript. LG acquired and analyzed the data.