The delicate balance between cell death and regeneration is crucial for human health and longevity. Most mechanisms involved in programmed cell death (PCD) play a key role in normal tissue renewal and repair after injury. At the same time, PCD can also disrupt regenerative processes, contributing to the development of pathological conditions such as cancer, fibrosis, neurodegenerative diseases, and other age-related disorders.
Researchers at the Institute of Environmental Medicine, Karolinska Institutet, have conducted an in-depth analysis of multilayered relationships to explore how cell death and regeneration interact. Their findings have been published in the leading journal Physiological Reviews.
"Cellular homeostasis is maintained by three essential physiological processes: proliferation, which increases the number of cells; differentiation, which can either increase or decrease cell numbers; and cell death, which removes cells. Two of these processes - proliferation and differentiation - are closely linked to regeneration." says Professor Emeritus Boris Zhivotovsky , one of the lead authors of the study.
Throughout the lifetime of a multicellular organism, its cells are constantly renewed, although the rate of turnover varies significantly between tissues. In a human lifetime, approximately three tons of cells are generated from hematopoietic stem cells (HSCs) in the bone marrow, even though these make up only about 1.5 kilograms of tissue. In postnatal tissues, there are three main mechanisms for generating new cells: proliferation of already specialized cells, activation and differentiation of stem cells (SCs), and reprogramming of differentiated cells.
For stem cells, maintaining a balance between preserving stemness and undergoing differentiation is particularly important - especially in aging and degenerative diseases, where the ability to retain a pool of multipotent cells is diminished.
"For many years, stem cell research has focused primarily on their self-renewal and differentiation, leaving the mechanisms of stem cell elimination relatively unexplored", says Boris Zhivotovsky. "While some studies have shown that cell death is necessary for effective regeneration, others suggest that regenerative capacity may be enhanced by inhibiting PCD. In our study, we present evidence that cell death and regeneration are not enemies or opposites. In our view, the human body can be seen as a 'self-renewing machine' with strong regenerative and repair potential, thanks to the well-regulated balance between cell death and cell generation."
Why does this matter?
The harmonious relationship between cell death and regeneration is of great importance to the rapidly growing and pioneering medical field of regenerative biomedicine. This area aims to control cell renewal processes and restore damaged organs and tissues. Understanding the body's endogenous mechanisms for cell death and regeneration opens promising avenues for developing new, nature-inspired strategies to maintain health and extend human life.
Publication
Programmed cell death and tissue regeneration: A link that should be resolved.
Kopeina GS, Efimenko AY, Tkachuk VA, Zhivotovsky B
Physiol Rev. 2025 18 juni. doi: 10.1152/physrev.00036.2024.
