According to an account written by Gonzalo Fernández de Oviedo in Historia General y Natural de las Indias (1535) Spanish explorer Juan Ponce de Leon (1474-1521), the first governor of Puerto Rico (then called Boriquien) attempted to discover the fountain of youth, a mystical spring that restored youth to everyone who drank of its waters. Although the legend originally pointed to Ethiopia based on Book III of The History of Herodotus, when the Greek historian (c. 484 BC-c. 425 BC) wrote in c. 440 BC – “The Icthyophagi [a term synonymous with coastal dwelling peoples] then in their turn questioned the king concerning the term of life, and diet of his people, and were told that most of them lived to be a hundred and twenty years old, while some even went beyond that age- they ate boiled flesh, and had for their drink nothing but milk. When the Icthyophagi showed wonder at the number of the years, [Egyptian Pharaoh Amasis (570 BC-526 BC)] led them to a fountain [in Ethiopia], wherein when they had washed, they found their flesh all glossy and sleek, as if they had bathed in oil- and a scent came from the spring like that of violets. The water was so weak, they said, that nothing would float in it, neither wood, nor any lighter substance, but all went to the bottom. If the account of this fountain be true, it would be their constant use of the water from it, which makes them so long-lived”[1] – later stories pointed to an island called Boinca located in Benini or Bimini, the westernmost district of the Bahamas. With Boinca in reach, Ponce de Leon made two attempts to locate the mystical fountain – one in 1513 and the other in 1521. Although accounts state he never found the fountain of youth, scientific evidence indicates he came tantalizingly close. Had he looked beneath the pristine Caribbean waters, he might have spotted a biologically immortal (absence of a sustained rising rate of mortality as the result of increasing chronological age as stated by the Gompertz-Makeham law of mortality) jellyfish, the Turritopsis nutricula, which with its gelatinous composition (96% water, 3% salt/other compounds, and 1% carbon and nitrogen), glossy, transparent bell-shape and ability to revert back into a younger state, is a living fountain of youth. However, it was not until March 1992 when Giorgio Bavestrello, Christian Somner, and Michele Sará published Bi-directional conversion in Turritopsis nutricula that this living fountain of youth was unveiled. Unlike other jellyfish that usually die after propagating, Turritopsis nutricula, a tiny solitary organism that preys on shrimp brine, microscopic plankton, zooplankton, and other tiny organisms, demonstrated “a unique case of ontogeny (the development of an individual organism from embryo to adult) reversal.” Turritopsis nutricula, which originated in the Caribbean (but has spread throughout the world’s oceans) is currently the only known organism where transdifferentiation (the irreversible transformation of cells from one differentiated type to another) takes place on an organismic level even though its individual parts, by themselves, are incapable of regeneration. Aside from Turritopsis nutricula’s transdifferentiation, the phenomenon which per C.D.M. Davey, Theory of Transdifferentiation (2 May 2006) “is a very rare event in nature,” generally occurs on an organic level when certain organisms such as newts and salamanders regenerate missing parts. In short, while switching of cell types occurs in rare instances, usually when an organism regenerates an organ or part, it is an integral phase in Turritopsis nutricula’s life cycle. With its ability to reverse the aging process – reverting back from a mature adult stage to immature polyp stage (its first stage of life) an indefinite number of times based on experimental results that indicated a 100% transformation rate based on a sample of 4000 Turritopsis nutricula medusae collected from the Gulf of Naples in the western Mediterranean from June 1993-October 1994, regardless of exposure to adverse conditions or type of stress factor or absence thereof as reported by Stefano Piraino, Ferdinando Boero, Brigitte Aeschbach, and Volker Schmid in Reversing the Life Cycle: Medusae Transforming into Polyps and Cell Transdifferentiation in Turritopsis nutricula (Cnidaria, Hydrozoa) (Biology Bulletin, June 1996) – Turritopsis nutricula has no natural limit to its lifespan since it can effectively regenerate its entire body. Turritopsis nutricula basically utilizes transdifferentiation to address environmental stress factors (e.g. increase/reduction in water temperature, reduction in salinity (salt-content), scarcity of food, and even senescence (biological aging)) and to repair physical/internal damage (e.g. parts of its body especially its bell are punctured or severed) regardless of stage. In addition, Turritopsis nutricula also engages in transdifferentiation following sexual activity regardless if stress conditions exist. Although Turritopsis nutricula’s transdifferentiation ability renders it biologically immortal, it is not naturally immortal per se. Like any jellyfish, it is subject to predation and disease (especially during the immature plankton stage; consequently, the majority of those that succumb perish prior to the medusa (mature) stage). However, since the latter poses a reduced risk, the population of Turritopsis nutricula is currently rising unchecked prompting Maria Pia Miglietta, Ph.D. of the Smithsonian Tropical Marine Institute to declare, “We are looking at a worldwide silent invasion.”[2] Jellyfish and Turritopsis nutricula Life Cycles: The typical jellyfish has a finite lifespan ranging from a few hours for smaller species to several months or even years for larger species. From the moment of inception, jellyfish typically undergo senescence with natural death ultimately resulting after propagation. Turritopsis nutricula, on the other hand, avoids senescence because transdifferentiation or reversion back to a younger state enables it to maintain efficient DNA repair capabilities, retain high levels of antioxidants, and minimize production of free radicals (harmful oxidants that damage an organism’s cellular ability to respond to homeostatic imbalances (loss of equilibrium), disease and other stress factors). In doing so, it avoids apoptosis or programmed cellular death. Transdifferentiation, which is a critical part of Turritopsis nutricula’s life cycle is described below: 1. Eggs develop in gonads (located in the stomach walls) of female Turritopsis nutricula. 2. Mature eggs are fertilized by sperm released in columns of water by male Turritopsis nutricula. 3. Fertilized eggs develop into planula larvae that settle on the sea floor and establish polyp colonies called hydroids. Each polyp relies on minute feeding tubes for sustenance. 4. Each polyp then produces a medusa (jellyfish) bud. 5. Within a few days, the medusae (approximately 1 mm in diameter with eight evenly spaced tentacles) break away from the hydroid colony. 6. Within 18-30 days the medusae attain sexual maturity contingent upon mean water temperature (18-22 days for a mean temperature of 72º F; 25-30 days for a mean temperature of 68º F). Upon reaching maturity, Turritopsis nutricula jellyfish range in size from approximately 4-5 mm and consist of between 80-90 tentacles. 7. Turritopsis nutricula then engages in reverse metamorphosis inverting or gradually contracting its bell with “intensive DNA replication occurring in the cells of the exumbrella, the endoderm of the radial canals and those of the subumbrellar plate endoderm” per Reversing the Life Cycle: Medusae Transforming into Polyps and Cell Transdifferentiation in Turritopsis nutricula (Cnidaria, Hydrozoa) (Biology Bulletin, June 1996). 8. Its tentacles and meogloea (the middle layer) then shrink and are resorbed as Turritopsis nutricula regresses into a cyst or blob of tissue, settling onto a substrate (surface on which an organism grows or is attached). 9. Turritopsis nutricula jellyfish then produce stolons that develop into polyps within a few days to form another hydroid colony. Afterwards, each polyp produces a medusa bud as the cycle resumes from step 4 only to be repeated over and over again due to sexual activity or exposure to stress, the latter which increases DNA replication, a key prerequisite of the transdifferentiation process. Conclusion: Scientists and geneticists are currently studying Turritopsis nutricula to discover its remarkable ability to reverse the aging process. Although the method Turritopsis nutricula uses remains unknown, the organism’s simplicity, genetic code (DNA could be structured to initiate reversion to polyp state when specific senescence, biological or stress conditions are met based on changes in chemical composition that could serve as a catalyst) potential partial (in which fusion of adult embryonic stem (ES) cells with pluripotent stem (PS) cells would like play a role in transdifferentiation) or complete retention of pluripotency (in which its entire stem cell count would consist of PS cells) may play a role. Turritopsis nutricula’s transdifferentiation ability, though, is not solely reliant on stem cells. Instead, it is believed that interstitial (differentiating stem cells) along with differentiating secretory (exumbrella or bell), digestive/circulatory (gastrovascular), and/or striated muscle cells also play a role.
Should researchers ultimately unravel the mystery of how Turritopsis nutricula engages in transdifferentiation, the secret to biological immortality could be attained ending the millennia-long and often perceived quixotic search for the fountain of youth. However, should such a development occur, the range of socio-economic, demographic, generational and even ethical (would lifespan be determined by government through euthanasia to respond to greater competition for limited, finite resources resulting from overpopulation?) issues that would ultimately have to be addressed would be staggering and perhaps impossible to resolve. Consequently, even if scientific research eventually solves the mystery of this living fountain of youth, humanity may be, figuratively speaking, forbidden from drinking of its waters to maintain socio-economic, generational and moral stability especially since the alternative might result in significant unintended consequences that could even lead to Armageddon and human extinction.
