Rejuvenation in invertebrates and their relevance for ageing biology.

Abstract

Ageing is not merely the progressive and irreversible accumulation of damage and a decline in biological function; it may also reflect the persistent and progressive dysregulation of developmental mechanisms during adulthood, leading to reduced stress resilience. This perspective has stimulated interest in rejuvenation, defined as the partial reversal of biological age, for example, through experimental reprogramming approaches such as heterochronic parabiosis or Yamanaka factor-based reprogramming. Although rejuvenation in mammals remains limited and requires strong experimental interventions, naturally occurring age-reversal phenomena have been described in several invertebrate metazoans, including ctenophores, cnidarians, platyhelminths, annelids and nematodes. This has been described either at the morphological level or at the physiological, cellular and/or molecular levels. Here, we review and synthesize studies documenting these inductive processes, with particular attention to terminology and to the distinction between 'morphological reversion' and multi-level 'rejuvenation' associated with potential lifespan extension. When available, we also summarize the associated molecular evidence and discuss how systematic and in-depth, multi-level studies of this naturally occurring phenomenon could provide new opportunities for ageing biology and rejuvenation strategies in mammals. This article is part of the theme issue 'Developmental circuits in ageing'.