Rejuvenation is a medical discipline focused on the practical reversal of the aging process. Rejuvenation is distinct from

life extension Life extension is the concept of extending the human life expectancy, lifespan, either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled oldest people, limit of 125 years. S ...

. Life extension strategies often study the causes of

aging Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...

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 Supernatural refers to phenomena or entities that are beyond the laws of nature. The term is derived from Medieval Latin , from Latin (above, beyond, or outside of) + (nature) Though the corollary term "nature", has had multiple meanings si ...

power can bring back youth and many mythical adventurers set out on a journey to do that, for themselves, their relatives or some authority that sent them anonymously. 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 Heaven or the heavens, is a common religious cosmological or transcendent supernatural place where beings such as deities, angels, souls, saints, or venerated ancestors are said to originate, be enthroned, or reside. According to the belie ...

. The stories continued well into the 16th century. The Spanish explorer

Juan Ponce de León Juan Ponce de León (, , , ; 1474 – July 1521) was a Spanish explorer and '' conquistador'' known for leading the first official European expedition to Florida and for serving as the first governor of Puerto Rico. He was born in Santervá ...

led an expedition around the

Caribbean islands Almost all of the Caribbean islands are in the Caribbean Sea, with only a few in inland lakes. The largest island is Cuba. Other sizable islands include Hispaniola, Jamaica, Puerto Rico and Trinidad and Tobago. Some of the smaller islands are re ...

and into Florida to find the Fountain of Youth. Led by the rumors, 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 Philosophy (from , ) is the systematized study of general and fundamental questions, such as those about existence, reason, knowledge, values, mind, and language. Such questions are often posed as problems to be studied or resolved. Some ...

, 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

child A child ( : children) is a human being between the stages of birth and puberty, or between the developmental period of infancy and puberty. The legal definition of ''child'' generally refers to a minor, otherwise known as a person younger ...

ren (sometimes literally sleeping, not necessarily having sex), bathing in or drinking their blood. The quest for rejuvenation reached its height with alchemy. All around 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. This was one of the first medically accepted rejuvenation therapies (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 a 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 Algiers ( ; ar, الجزائر, al-Jazāʾir; ber, Dzayer, script=Latn; french: Alger, ) is the capital and largest city of Algeria. The city's population at the 2008 Census was 2,988,145Census 14 April 2008: Office National des Statistiques ...

. Noteworthy people who had the surgery included Harold McCormick, chairman of the board of International Harvester Company, and the aging premier of Turkey. Swiss doctor

Paul Niehans Paul Niehans (21 November 18821 September 1971) was a Swiss surgeon, specialising in regenerative medicine, who was one of the developers of a cellular therapy called the Niehans method or fresh cell therapy. His renown grew through his treatme ...

, who was one of the fathers of cellular therapy, developed in 1931–1949 years the so-called Fresh cell therapy. Fresh cell therapy is mainly the use of live animal embryo organs cells which are injected into the patient with the purpose of achieving a revitalizing effect. These cells are generally extracted from sheep’s fetuses because in comparison to other animals, like pigs, rabbits and cows, sheep are clean animals and rarely contract diseases. Of course animal cells are not able to be included in human tissue, but they can secrete factors for rejuvenating. That's why this rejuvenation technology, despite the harsh criticism is practiced to this day. Rejuvenation technology and its effects on individuals and society have long been a subject of science fiction. The

Misspent Youth ''Misspent Youth'' is a 2002 science fiction novel by English author Peter F. Hamilton. Setting Set around 2040, it describes the story of Jeff Baker, an inventor who revolutionises the world by creating the ultimate method of information ...

and Commonwealth Saga by

Peter F. Hamilton Peter F. Hamilton (born 1960) is a British author. He is known for writing science fiction space opera. Biography Peter F. Hamilton was born in Rutland in 1960. He did not attend university. He said in an interview, "I did science at school ...

are among 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. The less perfect rejuvenation featured in the Mars trilogy by Kim Stanley Robinson results in long-term memory loss and sheer boredom that comes with extreme age. The post-mortal characters in the Revelation Space series have long-term or essentially infinite lifespans, and sheer boredom induces them to undertake activities of extreme risk.

Modern developments

Aging Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...

is the accumulation of damage to

macromolecule A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

, tissues and organs in and on the body which, when it can no longer be tolerated by an organism, ultimately leads to its death. 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

. A few experimental methods such as replacing hormones to youthful levels have had considerable success in partially rejuvenating laboratory animals and humans. A 2011 experiment involved breeding genetically manipulated mice that lacked an enzyme called telomerase, causing the mice to age prematurely and suffer ailments. When the mice were given injections to reactivate the enzyme, it repaired the damaged tissues and reversed the signs of aging. There are at least eight important hormones that decline with age: 1.

human growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...

(HGH); 2. the sexual hormones: testosterone or oestrogen/progesterone; 3.

erythropoietin Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bo ...

(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. In line with this, recent experiments show that heterochronic parabiosis, i.e. connecting the circulatory systems of young and old animal, leads to the rejuvenation of the old animal, including restoration of proper stem cell function. Similar experiments show that grafting old muscles into young hosts leads to their complete restoration, whereas grafting young muscles into old hosts does not. These experiments show that aging is mediated by systemic environment, rather than being an intrinsic cell property. Clinical trials based on transfusion of young blood were scheduled to begin in 2014. Another intervention that is gaining popularity is epigenetic reprogramming. Through the use of Yamanaka factors, aged cells can revert to a younger state. Most attempts at genetic repair have traditionally involved the use of a

retrovirus A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase ...

to insert a new gene into a random position on a chromosome. But by attaching zinc fingers (which determine where transcription factors bind) to

endonuclease Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain. Some, such as deoxyribonuclease I, cut DNA relatively nonspecifically (without regard to sequence), while many, typically called restriction endonucleases ...

s (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 cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...

s from the

bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...

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. Enhanced DNA repair has been proposed as a potential rejuvenation strategy. Stem cell regenerative medicine uses three different strategies: # Implantation of

s from culture into an existing tissue structure # Implantation of stem cells into a tissue scaffold that guides restoration # Induction of residual

of a tissue structure to regenerate the necessary body part A salamander can not only regenerate a

limb Limb may refer to: Science and technology * Limb (anatomy), an appendage of a human or animal *Limb, a large or main branch of a tree *Limb, in astronomy, the curved edge of the apparent disk of a celestial body, e.g. lunar limb *Limb, in botany, ...

, but can regenerate the lens or retina of an

eye Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...

and can regenerate an

intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...

. For regeneration the salamander tissues form a

blastema A blastema (Greek ''βλάστημα'', "offspring") is a mass of cells capable of growth and regeneration into organs or body parts. The changing definition of the word "blastema" has been reviewed by Holland (2021). A broad survey of how blast ...

by de-differentiation of

mesenchymal cells Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage c ...

, and the

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 Plastic surgery is a surgical specialty involving the restoration, reconstruction or alteration of the human body. It can be divided into two main categories: reconstructive surgery and cosmetic surgery. Reconstructive surgery includes craniofa ...

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 commonly found throughout history, many fake rejuvenation products that have been shown to be ineffective. Chief among these are powders, sprays, gels, and homeopathic substances that claim to contain growth hormones. Authentic growth hormones are only effective when injected, mainly due to the fact that the 191-amino acid protein is too large to be absorbed through the mucous membranes, and would be broken up in the stomach if swallowed. The Mprize scientific competition is under way to deliver on the mission of extending healthy human life. It directly accelerates the development of revolutionary new life extension therapies by awarding two cash prizes: one to the research team that breaks the world record for the oldest-ever mouse; and one to the team that develops the most successful late-onset rejuvenation. Current Mprize winner for rejuvenation is Steven Spindler. Caloric restriction (CR), the consumption of fewer calories while avoiding malnutrition, was applied as a robust method of decelerating aging and the development of

age-related diseases An aging-associated disease (commonly termed age-related disease, ARD) is a disease that is most often seen with increasing frequency with increasing senescence. They are essentially complications of senescence, distinguished from the aging proc ...

Strategies for engineered negligible senescence

The biomedical

gerontologist Gerontology ( ) is the study of the social, cultural, psychological, cognitive, and biological aspects of aging. The word was coined by Ilya Ilyich Mechnikov in 1903, from the Greek , ''geron'', "old man" and , ''-logia'', "study of". The fiel ...

Aubrey de Grey has initiated a project, strategies for engineered negligible senescence (SENS), to study how to reverse the damage caused by aging. He has proposed seven strategies for what he calls the seven deadly sins of aging: # Cell loss can be repaired (reversed) just by suitable

exercise Exercise is a body activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons, to aid growth and improve strength, develop muscles and the cardiovascular system, hone athletic ...

in the case of

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

. For other tissues it needs various growth factors to stimulate cell division, or in some cases it needs stem cells. # Senescent

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. # Protein cross-linking can largely be reversed by

drugs A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalat ...

that break the links. But to break some of the cross-links we may need to develop enzymatic methods. # Extracellular garbage (like amyloid) can be eliminated by vaccination that gets immune cells to "eat" the garbage. # 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. # For

mitochondrial A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...

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 The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...

by gene therapy. The

mitochondrial DNA Mitochondrial DNA (mtDNA or mDNA) is the DNA located in mitochondria, cellular organelles within eukaryotic cells that convert chemical energy from food into a form that cells can use, such as adenosine triphosphate (ATP). Mitochondrial D ...

experiences a high degree of mutagenic damage because most

free radicals In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spont ...

are generated in the

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

. 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. # 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. In 2009, Aubrey de Grey co-founded the SENS Foundation to expedite progress in the above-listed areas.

Scientific journal

* '' Rejuvenation Research'' Editor: Aubrey de Grey. Publisher:

Mary Ann Liebert, Inc. Mary Ann Liebert, Inc. is a privately held independent publishing company founded by its president, Mary Ann Liebert, in 1980. The company publishes peer-reviewed academic journals, books, and trade magazines in the areas of biotechnology, biom ...

ISSN 1549-1684 – Published Bimonthly.

References

External links