Researchers from the National Institutes of Health (NIH) and their collaborators have made significant discoveries about healing and aging by studying a small sea creature called Hydractinia symbiolongicarpus. This tube-shaped animal, found on hermit crab shells, has the remarkable ability to regenerate an entirely new body from just its mouth. By sequencing the RNA of the Hydractinia during the early stages of regeneration, the researchers identified a molecular signature associated with the process of aging, or senescence.
The findings, published in Cell Reports, indicate a close connection between the fundamental biological processes of healing and aging, shedding new light on the evolution of aging. Charles Rotimi, Ph.D., director of the Intramural Research Program at the National Human Genome Research Institute (NHGRI), emphasized the significance of studying unusual organisms like Hydractinia, as they reveal both the universal nature of many biological processes and the gaps in our understanding of their functions, relationships, and evolution. These findings hold immense potential for providing fresh insights into human biology.
Untangling the evolutionary origins of essential biological processes like healing and aging is crucial for comprehending human health and disease. While humans possess some regenerative capabilities, such as healing broken bones or regrowing damaged livers, other animals like salamanders and zebrafish can regenerate entire limbs and various organs. Interestingly, organisms with simpler body structures, such as Hydractinia, often exhibit the most extreme regenerative abilities, being able to grow an entirely new body from a fragment of tissue.
The discovery of a regenerative role for senescence in Hydractinia challenges previous findings in human cells. In humans, senescent cells tend to remain senescent, leading to chronic inflammation and accelerating aging in neighboring cells. Andy Baxevanis, Ph.D., a senior scientist at NHGRI and one of the study’s authors, highlighted that most studies on senescence in humans are linked to chronic inflammation, cancer, and age-related diseases. By studying animals like Hydractinia, we can gain insights into the potential benefits of senescence and expand our understanding of aging and healing.
Earlier research had already revealed that Hydractinia possesses a unique group of stem cells responsible for regeneration. Stem cells have the capacity to differentiate into various cell types, making them instrumental in creating new body parts.
While stem cells in humans primarily play a role in development, organisms like Hydractinia demonstrate the use of stem cells throughout their lives due to their high regenerative capabilities. In Hydractinia, the key stem cells responsible for regeneration are stored in the lower trunk of the body. However, researchers discovered that when they removed the mouth, a distant part from where the stem cells reside, a new body grew.
Unlike human cells, which are committed to their specific fates, adult cells in highly regenerative organisms can revert back to stem cells when the organism is injured, although the exact mechanisms behind this process remain unclear. Based on this observation, the researchers speculated that Hydractinia must generate new stem cells and sought molecular signals that might be involved in directing this process.
During RNA sequencing, the researchers found indications of senescence, leading them to search the genome of Hydractinia for sequences resembling those of senescence-related genes found in humans. They identified three genes, one of which was activated in cells near the site of the animal’s injury. Deleting this gene prevented the development of senescent cells, consequently hindering the generation of new stem cells and impeding the regeneration process.
To understand how Hydractinia overcomes the detrimental effects of senescence, the researchers observed that the animals expelled the senescent cells from their mouths. While humans cannot eliminate aging cells as easily, the roles of senescence-related genes in Hydractinia provide insights into the evolutionary process of aging.
Considering that humans and Hydractinia shared a common ancestor more than 600 million years ago, and these organisms do not experience aging, studying Hydractinia and its relatives, such as jellyfish and corals, becomes crucial in understanding our earliest animal ancestors. The researchers hypothesize that regeneration may have been the original function of senescence in the first animals.
Dr. Baxevanis commented on the research, stating that we still lack a comprehensive understanding of how senescent cells trigger regeneration or how widespread this process is in the animal kingdom. Nonetheless, studying these distant animal relatives enables us to uncover some of the secrets behind regeneration and aging, which could have implications for regenerative medicine and the study of age-related diseases.