Planarians Undergo Rejuvenation When Regrowing Lost Tissues
Some lower animal species are capable of exceptional feats of regeneration. Planarians are capable of regrowing an entire new body after being cut in half, for example. One way of thinking about this is that some of these species blur the line between developmental growth and regeneration. Adults make continued use of processes that occur during development, unlike most higher animals. One of the interesting aspects of early development is that adult germline cells undergo rejuvenation, shedding age-related changes in gene expression. Here, researchers show that adult planarians are in fact undergoing rejuvenation while they regrow lost body parts.
Long-lived species provide unique opportunities to uncover naturally evolved mechanisms for the extension of healthspan and lifespan. Freshwater planarians are commonly referred to as immortal due to their extremely long lifespan and unique tissue regeneration capabilities. It was reported that telomeres shorten, eyes change, and viable progeny decline in older planarians. Whether planarians experience aging and show a typical age-dependent decline in physiological, cellular and molecular functions has not been systematically examined, in part because of the challenges inherent in measuring lifespan in a long-lived animal, or even defining age in asexual planarians that undergo a vegetative mode of reproduction.
Inbred lines of the sexual lineage of S. mediterranea have been established to study genetic variations and chromosome biology. This resource provides a unique opportunity to examine aging in this long-lived model system and disentangle genetic control from environmental effects. To use this model for aging research, we define chronological age as time since fertilization, thus overcoming the challenges involved in lineages that rely on vegetative reproduction.
Here we report that the sexual lineage of S. mediterranea exhibits physiological decline within 18 months of birth, including altered tissue architecture, impaired fertility and motility, and increased oxidative stress. Single-cell profiling of young and older planarian heads uncovered loss of neurons and muscle, increase of glia, and revealed minimal changes in pluripotent stem cells, along with molecular signatures of aging across tissues. Remarkably, amputation followed by regeneration of lost tissues in older planarians led to reversal of these age-associated changes in tissues both proximal and distal to the injury at physiological, cellular, and molecular levels. Our work suggests mechanisms of rejuvenation in both new and old tissues concurring with planarian regeneration, which may provide valuable insights for antiaging interventions.
Of course regeneration will involve rejuvenation. The cells have to de-differentiate in order to become pluropotent enough to regenerate various tissues. This de-differentiation process by definition will reverse epigenetics (and mitochondrial) aging in the process of occurring.