Rejuvenation

Introduction
Rejuvenation is the procedure of reversing the aging process, thus regaining youth. As people get older, their health worsens, strength and intelligence generally diminish, and beauty is thought by many to go away.

Rejuvenation is distinct from life extension. Life extension strategies often study the causes of aging and try to oppose those causes in order to slow aging. Rejuvenation is the reversal of aging and thus requires a different strategy, namely repair of the damage that is associated with aging or replacement of damaged tissue with new tissue. Rejuvenation can be a means of life extension, but most life extension strategies do not involve rejuvenation.

Historical and Cultural Background
Various myths tell the stories about the quest for rejuvenation. It was believed that magic or intervention of a supernatural power can bring back the youth and many mythical adventurers set out on a journey to do that, for themselves, their relatives or some authority that sent them.

An ancient Chinese emperor actually sent out ships of young men and women to find a pearl that would rejuvenate him. This led to a myth among modern Chinese that Japan was founded by these people.

In some religions people were to be rejuvenated after death prior to placing them in heaven.

The stories continued well into the 16th century. A famous Spanish explorer Juan Ponce de León led the expedition around the Caribbean islands and into Florida to find the Fountain of Youth. Led by the rumours, the expedition continued the search and many perished. The Fountain was nowhere to be found as locals were unaware of its exact location.

Since the emergence of philosophy, sages and self-proclaimed wizards always made enormous efforts to find the secret of youth, both for themselves and for their noble patrons and sponsors. It was widely believed that some potions may restore the youth.

Another commonly cited approach was attempting to transfer the essence of youth from young people to old. Some examples of this approach were sleeping with virgins or children (sometimes literally sleeping, not necessarily having sex), bathing in or drinking their blood.

The quest for rejuvenation reached its height with Alchemy. All around the Europe and also beyond alchemists were looking for the Philosopher's Stone, the mythical substance that, as it was believed, could not only turn lead into gold, but also prolong life and restore youth. Although the set goal was not achieved, Alchemy paved the way to the scientific method and so to the medical advances of today.

Serge Abrahamovitch Voronoff was a French surgeon born in Russia who gained fame for his technique of grafting monkey testicle tissue on to the testicles of men while working in France in the 1920s and 1930s. Which was one of the first medically accepted Rejuvenation Therapy (before he was proved to be wrong around 1930-1940). The technique brought him a great deal of money, although he was already independently wealthy. As his work fell out of favor, he went from being highly respected surgeon to a subject of ridicule. By the early 1930s, over 500 men had been treated in France by his rejuvenation technique, and thousands more around the world, such as in a special clinic set up in Algiers. Noteworthy people who had the surgery included Harold McCormick, chairman of the board of International Harvester Company, and the ageing premier of Turkey.

In fiction, there is an increasing amount of work being done on possibilities of rejuvenation treatments, and the effect this would have on society. Misspent Youth as well as the Commonwealth Saga by Peter F. Hamilton are one of the most well known examples of this, dealing with the short and long term effects of a near perfect 80 year old to 20 year old body change with mind intact. Also the Mars trilogy deals with a much more imperfect type of rejuvenation, including problems such as long term memory loss and sheer boredom that comes with such age. Also the post mortal characters in the Revelation Space series often illustrate this issue with long term or essentially infinite lifespans, sheer boredom induces them to undertake activities of extreme risk.

Ancient developments
The dream of longevity is a common heritage of humanity. The ancient researchers and practitioners of Siddha Vaidya in the east had developed strategies for the same reason, some of which were very effective. Our current understanding of biology, physiology, immunology and biochemistry is helping us to decipher the rationale of these therapies. Ranging from detoxification of the body to targeted nutrition these therapies can even produce invivo stimulation and deferentiation of stem cells into useful mature cells. Many of these longevity techniques are still practiced in South India.

Modern developments
Aging is an accumulation of damage to macromolecules, cells, tissues and organs. If any of that damage can be repaired, the result is rejuvenation.

There have been many experiments which have been shown to increase the maximum life span of laboratory animals, thereby achieving life extension. A few experimental methods such as replacing hormones to youthful levels have had considerable success in partially rejuvenating laboratory animals and humans. There are at least eight important hormones that decline with age: 1. human growth hormone (HGH); 2. the sexual hormones: testosterone or estrogen/progesterone; 3. erithropoietin EPO; 4. insulin; 5. DHEA; 6. melatonin; 7. thyroid; 8. pregnenolone. In theory, if all or some of these hormones are replaced, the body will respond to them as it did when it was younger, thus repairing and restoring many body functions. This seems to be borne out in hundreds of thousands of persons who have replaced hormones for many years, especially human growth hormone (HGH, a.k.a. GH). Most attempts at genetic repair have traditionally involved the use of a retrovirus to insert a new gene into a random position on a chromosome. But by attaching zinc fingers (which determine where transcription factors bind) to endonucleases (which break DNA strands) homologous recombination can be induced to correct and replace defective (or undesired) DNA sequences. The first applications of this technology are to isolate stem cells from the bone marrow of patients having blood disease mutations, to correct those mutations in laboratory dishes using zinc finger endonucleases and to transplant the stem cells back into the patients.

Regenerative medicine uses three different strategies:
 * 1) Implantation of stem cells from culture into an existing tissue structure
 * 2) Implantation of stem cells into a tissue scaffold that guides restoration or
 * 3) Induction of residual cells of a tissue structure to regenerate the necessary body part.

A salamander can not only regenerate a limb, but can regenerate the lens or retina of an eye and can regenerate an intestine. For regeneration the salamander tissues form a blastema by de-differentiation of mesenchymal cells, and the blastema functions as a self-organizing system to regenerate the limb.

Yet another option involves cosmetic changes to the individual to create the appearance of youth. These are generally superficial and do little to make the person healthier or live longer, but the real improvement in a person's appearance may elevate their mood and have positive side effects normally correlated with happiness. Cosmetic surgery is a large industry offering treatments such as removal of wrinkles ("face lift"), removal of extra fat (liposuction) and reshaping or augmentation of various body parts (abdomen, breasts, face).

There are also, as always in history, many fake rejuvenation products that do not work. Chief among these are powders and sprays and gels and homeopathic that claim to be "growth hormone". Authentic growth hormone can only be injected, because the 191 amino-acid protein is too large to be absorbed through the mucous membranes, and would break up in the stomach if it is swallowed.

Eastern medical approaches offers us yet another treasure of techniques that can be used for tissue regeneration and invivo stem cell evolution and stimulation. According to Rajkumar Reghunathan, the inbuilt mechanism of inflammation and repair holds many keys for tissue renovation.

Strategies for Engineered Negligible Senescence (SENS)
The leading modern exponent of scientific rejuvenation is the biomedical gerontologist Dr. Aubrey de Grey. He calls his project to reverse the damage we call aging "SENS" (Strategies for Engineered Negligible Senescence). He has proposed seven strategies for what he calls the "seven deadly sins":


 * 1) Cell loss can be repaired (reversed) just by suitable exercise in the case of muscle. For other tissues it needs various growth factors to stimulate cell division, or in some cases it  needs stem cells.
 * 2) Senescent cells,  can be removed by activating the immune system against them. Or they can be destroyed by gene therapy to introduce "suicide genes" that only kill senescent cells.
 * 3) Protein cross-linking can largely be reversed by drugs that break the links. But to break some of the cross-links we may need to develop enzymatic methods.
 * 4) Extracellular garbage (like amyloid) can be eliminated by vaccination that gets immune cells to "eat" the garbage.
 * 5) For intracellular junk we need to introduce new enzymes, possibly enzymes from soil bacteria, that can degrade the junk (lipofuscin) that our own natural enzymes cannot degrade.
 * 6) For mitochondrial mutations the plan is not to repair them but to prevent harm from the mutations by putting suitably modified copies of the mitochondrial genes into the cell nucleus by gene therapy. The mitochondrial DNA experiences a high degree of mutagenic damage because most free radicals are generated in the mitochondria. A copy of the mitochondrial DNA located in the nucleus will be better protected from free radicals, and there will be better DNA repair when damage occurs. All mitochondrial proteins would then be imported into the mitochondria.
 * 7) For cancer (the most lethal consequence of mutations) the strategy is to use gene therapy to delete the genes for telomerase and to eliminate telomerase-independent mechanisms of turning normal cells into "immortal" cancer cells. To compensate for the loss of telomerase in stem cells we would introduce new stem cells every decade or so.

Dr. de Grey has created the Methuselah Mouse Prize, which awards money to researchers who can rejuvenate mice.

Scientific Journal

 * Rejuvenation Research Editor: Aubrey de Grey. Publisher: Mary Ann Liebert, Inc. ISSN 1549-1684 - Published Quarterly.

Strategies for Engineered Negligible Senescence

 * Strategies for Engineered Negligible Senescence (SENS)

Other

 * American Academy of Anti-Aging Medicine
 * Regenerative Medicine and Rejuvenation
 * Life Extension magazine interview about rejuvenation science
 * Resources and Articles on the Biology of Aging and Life-Extension

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