The regeneration capacity of the flatworm Macrostomum lignano—on repeated regeneration, rejuvenation, and the minimal size needed for regeneration

Abstract

The lion's share of studies on regeneration in Plathelminthes (flatworms) has been so far carried out on a derived taxon of rhabditophorans, the freshwater planarians (Tricladida), and has shown this group's outstanding regeneration capabilities in detail. Sharing a likely totipotent stem cell system, many other flatworm taxa are capable of regeneration as well. In this paper, we present the regeneration capacity of Macrostomum lignano, a representative of the Macrostomorpha, the basal-most taxon of rhabditophoran flatworms and one of the most basal extant bilaterian protostomes. Amputated or incised transversally, obliquely, and longitudinally at various cutting levels, M. lignano is able to regenerate the anterior-most body part (the rostrum) and any part posterior of the pharynx, but cannot regenerate a head. Repeated regeneration was observed for 29 successive amputations over a period of almost 12 months. Besides adults, also first-day hatchlings and older juveniles were shown to regenerate after transversal cutting. The minimum number of cells required for regeneration in adults (with a total of 25,000 cells) is 4,000, including 160 neoblasts. In hatchlings only 1,500 cells, including 50 neoblasts, are needed for regeneration. The life span of untreated M. lignano was determined to be about 10 months.

Resilience to aging in the regeneration‐capable flatworm Macrostomum lignano

“…Moreover, the gene expression data demonstrate the dominant effect of age over single or multiple regeneration. This is in contrast with the previous observations (Egger et al., 2006) showing lifespan extension due to repeated regeneration. The maximum lifespan of 10 months of the uncut control group of that experiment is, however, remarkably short compared to the later published (Mouton et al., 2009) and here obtained lifespans showing that worms are able to live over 2 years.…”

“…In sexual species, uncoupling of regeneration from reproduction might have led to a loss of the rejuvenating abilities. One should, however, keep in mind that even in sexual flatworms, there is no strict separation between germline and soma, as amputated heads can regenerate the gonads (Egger et al., 2006). Maybe not surprising, we found an overrepresentation of transcripts enriched in proliferating germline cells within the small group of transcripts with a long‐lasting change in expression after regeneration.…”

“…As a consequence, repeated rejuvenation can potentially lead to immortality. While the original experiments by Child (Child, 1915) and Hyman (Hyman, 1919) were debated due to contradictory results (Allen, 1919; Brøndsted, 1969; Pedersen, 1956), several observations of an extended lifespan after regeneration further popularized the rejuvenation hypothesis (Egger, Ladurner, Nimeth, Gschwentner & Rieger, 2006; Haranghy & Balázs, 1964). Poorly defined culture conditions and potential non‐age‐related causes of mortality might, however, create some doubt about these findings.…”

“…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). Macrostomum is able to regenerate missing body parts anteriorly, posteriorly, and laterally, although the presence of the brain and pharynx is obligatory.…”

“…Macrostomum is able to regenerate missing body parts anteriorly, posteriorly, and laterally, although the presence of the brain and pharynx is obligatory. Interestingly, somatic neoblasts are able to regenerate functional gonads, indicating the lack of a strict separation between soma and germline (Egger et al., 2006). Previously, it was shown that M. lignano ages (Mouton, Willems, Back, Braeckman & Borgonie, 2009) and that repeated amputations might extend the lifespan (Egger et al., 2006).…”