Abstract
SummaryAnimals 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.
Highlights
During the last decade, the large diversity of age-related changes and life trajectories of different animals became increasingly clear (Jones et al, 2014)
We found that regeneration does not affect the aging of M. lignano, but that this worm evolved mechanisms to attenuate its aging process
In contrast to M. lignano, genome maintenance genes are significantly underrepresented among genes upregulated with age in all models, and even enriched among genes downregulated with age in zebrafish skin (Table 1). These findings indicate that gene expression undergoes temporal changes in M. lignano, which are at least partly due to aging, but the aging profile is very different from conventional models, such as C. elegans, mouse, and zebrafish
Summary
The large diversity of age-related changes and life trajectories of different animals became increasingly clear (Jones et al, 2014). Already at the start of the 20th century, it was suggested that flatworms age, but are able to reverse the aging process (rejuvenate) through regeneration of the body after amputation or fission (Child, 1915). The worms have a large mesodermal population of proliferating cells, called neoblasts, which can form every cell type in the body (Ladurner et al, 2008) These neoblasts enable a high cellular turnover during homeostasis and a remarkable regeneration capacity (Egger et al, 2006; Ladurner et al, 2008). We tested the rejuvenation hypothesis in M. lignano by characterizing survival, morphology, fertility, and gene expression as a function of age in intact, and single and multiple regenerated worms. The generated temporal gene expression profile of M. lignano provides an insight into these mechanisms and will serve as a valuable resource for aging research
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