Programmed cell death plays a crucial role during tissue turnover in all animal species, and it is also essential during regeneration, serving as a key signalling mechanism to promote tissue repair and regrowth. Apoptosis is a form of programmed cell death essential for maintaining tissue health and regeneration by systematically dismantling damaged or unnecessary cells while avoiding harm to neighboring tissues. This process ensures proper development, eliminates potentially harmful cells, and contributes to tissue remodeling. In addition to apoptosis, other forms of cell death, such as autophagy-dependent cell death, support regeneration and homeostasis by clearing cellular debris and recycling components for energy and repair. With ongoing research, scientists continue to uncover new types of cell death, revealing a complex landscape of mechanisms that contribute to cellular balance and organismal health.

In this study we compare cell death processes occurring in two animal species that show essentially different live cycle and regenerative abilities, such as planarians and Drosophila. Freshwater planarians show a striking plasticity in their adult stage. They are able to regenerate any body part, including an entire head, within just a few days. They also continuously adjust their body size in response to nutritional availability [1], [2], [3]. These abilities rely on the presence of an abundant population of adult stem cells, known as neoblasts, which are distributed throughout the planarian body and can replace any cell type. Neoblasts are the only proliferative cell type in planarians and are responsible for giving rise to all the various cell types within the planarian body [4], [5]. As a result, planarians experience a high rate of somatic cell turnover throughout their life, offering a unique opportunity to study the mechanisms and regulation of cell turnover in adult tissues. There are evidences that cell death is present during the entire regeneration process indicating its continuous role in tissue remodeling and repair [6], [7], [8]. Regeneration and tissue homeostasis rely on a delicate balance between cell proliferation and cell death, but, despite conservation of molecular pathways, mechanisms responsible for cell death in planarians have remained elusive [9].

Drosophila melanogaster does not possess the extensive regenerative abilities observed in some other species, but certain developing and adult tissues are capable of regeneration [10]. Drosophila is also a valuable model due to its powerful genetic tools, well-understood developmental biology and the ability to visualize cell death at specific lifecycle stages, advantages not yet possible in planarians [10], [11]. In Drosophila, cell death is essential for development, metamorphosis, and maintaining adulthood homeostasis. During development, programmed cell death removes unnecessary or misplaced cells, shaping tissues and organ structures. In metamorphosis, apoptosis and autophagy eliminate larval tissues that are not retained in the adult, making room for new structures. After metamorphosis, cell death in specific tissues, like the brain and muscles, helps complete maturation [12]. In adulthood, cell death is limited to tissue maintenance rather than large-scale remodeling.

The role of cell death in regeneration and tissue turnover extends beyond planarians and Drosophila and has been well-documented in other sources, which we recommend to the reader. For example, similar mechanisms are observed in other organisms, such as zebrafish [13], Hydra [14], Xenopus tadpoles [15] or some mammalian organs, including skin, gut, kidney, and muscle [16]. Also, much information of cell death processes and regeneration is available for other insect orders such as Lepidoptera, Orthoptera, and Coleoptera [17].

This review explores the types of cell death involved in cell renewal and regeneration in planarians and Drosophila, highlighting the similarities and differences in their roles. It also examines the signalling pathways that play a key role, such as the JNK and PI3K/Akt pathways, both of which are shared between these two species. Our goal is to provide an overview of the current understanding of this process, highlighting key topics from these two model systems and considering their potential implications for other organisms and tissues.