Dataset Information

Resilience to aging in the regeneration-capable flatworm Macrostomum lignano.

ABSTRACT: 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.

SUBMITTER: Mouton S

PROVIDER: S-EPMC5946080 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Resilience to aging in the regeneration-capable flatworm Macrostomum lignano.

Mouton Stijn S Grudniewska Magda M Glazenburg Lisa L Guryev Victor V Berezikov Eugene E

Aging cell 20180228 3

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 repor ...[more]

PMID: 29488325

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Project description:BackgroundMacrostomum lignano is a small free-living flatworm capable of regenerating all body parts posterior of the pharynx and anterior to the brain. We quantified the cellular composition of the caudal-most body region, the tail plate, and investigated regeneration of the tail plate in vivo and in semithin sections labeled with bromodeoxyuridine, a marker for stem cells (neoblasts) in S-phase.ResultsThe tail plate accomodates the male genital apparatus and consists of about 3,100 cells, about half of which are epidermal cells. A distinct regeneration blastema, characterized by a local accumulation of rapidly proliferating neoblasts and consisting of about 420 cells (excluding epidermal cells), was formed 24 hours after amputation. Differentiated cells in the blastema were observed two days after amputation (with about 920 blastema cells), while the male genital apparatus required four to five days for full differentiation. At all time points, mitoses were found within the blastema. At the place of organ differentiation, neoblasts did not replicate or divide. After three days, the blastema was made of about 1420 cells and gradually transformed into organ primordia, while the proliferation rate decreased. The cell number of the tail plate, including about 960 epidermal cells, was restored to 75% at this time point.ConclusionRegeneration after artificial amputation of the tail plate of adult specimens of Macrostomum lignano involves wound healing and the formation of a regeneration blastema. Neoblasts undergo extensive proliferation within the blastema. Proliferation patterns of S-phase neoblasts indicate that neoblasts are either determined to follow a specific cell fate not before, but after going through S-phase, or that they can be redetermined after S-phase. In pulse-chase experiments, dispersed distribution of label suggests that S-phase labeled progenitor cells of the male genital apparatus undergo further proliferation before differentiation, in contrast to progenitor cells of epidermal cells. Mitotic activity and proliferation within the blastema is a feature of M. lignano shared with many other regenerating animals.

Dataset Information

Resilience to aging in the regeneration-capable flatworm Macrostomum lignano.

Publications

Resilience to aging in the regeneration-capable flatworm Macrostomum lignano.

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