Crispy sea creature rewrites science

A relative of jellyfish and corals can regenerate its entire body with the help of „aging” cells.

Researchers from the National Institutes of Health and their colleagues have made new discoveries about healing and aging by studying a tiny sea creature capable of regenerating its entire body using its mouth. They analyzed RNA sequence Hydractinia symbiolongicarpusA small, tube-shaped animal organism that lives in the shells of hermit crabs.

Just like that Hydractinia As new bodies began to regenerate, researchers discovered a molecular signature associated with the biological process of aging, also known as senescence. According to a study published in Cell reports, Hydractinia It demonstrates that the basic biological processes of healing and aging are intertwined, providing a new perspective on how aging evolved.

„Studies like these that explore the biology of unusual organisms reveal how universal many biological processes are and how much we still don’t understand about their functions, relationships, and evolution,” said Intramural Director Charles Rotimi. research program at the National Human Genome Research Institute (NHGRI), part of the NIH. „Such findings have great potential to provide novel insights into human biology.”

Hydractinia’s regeneration-driven stem cells are stored in the lower trunk of the animal’s body, far from the mouth. Credit: Darryl Leja, National Human Genome Research Institute (NHGRI)

Unraveling the evolutionary origins of fundamental biological processes such as aging and healing is essential to understanding human health and disease. Humans have the ability to regenerate, such as healing a broken bone or regrowing a damaged liver. A few other animals, such as salamanders and zebrafish, can replace entire limbs and fill different organs. However, animals with simple bodies such as HydractiniaOften possessing extreme regenerative abilities, such as growing a whole new body from a single piece of tissue.

A regenerative role for senescence is at odds with findings in human cells. „Most of the research on aging has been related to chronic inflammation, cancer and age-related diseases,” said Andy Paxevanis, PhD, senior scientist at NHGRI and author of the study. „Normally, in humans, mature cells are senescent, and these cells cause chronic inflammation and induce aging in nearby cells. From animals like HydractiniaWe can learn about how aging can be beneficial and expand our understanding of aging and healing.

Earlier, researchers found that Hydractinia Contains specialized stem cells for regeneration. Stem cells can transform into other types of cells and are therefore useful in making new body parts. In humans, stem cells function mainly in development, but are preferred in highly regenerative organisms Hydractinia Stem cells are used throughout their lives. Hydractinia It stores its regeneration-driven stem cells in the lower trunk of its body.

However, when researchers remove the mouth — far from the area where the stem cells reside — the mouth grows a new body. Unlike human cells, which are locked in their fates, adult cells of some highly regenerative organisms can become stem cells when the organism is injured, although this process is not well understood. So the researchers assume that Hydractinia We need to generate new stem cells and look for molecular signals that can drive this process.

When RNA sequencing indicated maturation, the researchers scanned the genome Hydractinia For sequences such as aging-related genes in humans. Of the three genes they found, one was „turned on” in cells near where the animal was cut. When the researchers deleted this gene, the animals’ ability to make mature cells was blocked, and without the mature cells, the animals did not make new stem cells and could not regenerate.

The researchers monitored the mature cells Hydractinia To find out how this animal avoids the harmful effects of aging. Unexpectedly, the animals expelled mature cells from their mouths. Although humans cannot easily eliminate senescent cells, the role of aging-related genes Hydractinia Suggest how the aging process evolved.

As humans we shared the last common ancestor Hydractinia – and its close relatives, jellyfish and corals – 600 million years ago, and these animals have not aged. Due to these factors, Hydractinia It can provide important insights into our earliest animal ancestors. Therefore, the researchers hypothesize that regeneration may have been an original function of maturation in the first animals.

„We still don’t understand how mature cells trigger regeneration or how widespread this process is in the animal kingdom,” said Dr. Paxevanis. „Fortunately, by studying some of our distant animal relatives, we can begin to unravel some of the mysteries of regeneration and aging—which could ultimately advance the field of regenerative medicine and the study of age-related diseases.”

Reference: Miguel Salinas-Saavetra, Gabriel Febrimarza, Helen R. Krasovec, Andreas D. Horgan and Yuri Baksevanis, “Senescence-induced cellular reprogramming for cnidarian whole-body regeneration,” 30 June 2023. Cell reports.
DOI: 10.1016/j.celrep.2023.112687