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A geroprotector is a senotherapeutic that aims to affect the root cause of aging and age-related diseases, and thus prolong the life span of animals. [1] [2] Some possible geroprotectors include melatonin, [3] carnosine, [4] metformin, [5] rapamycin, [6] nicotinamide mononucleotide (NMN) [7] and delta sleep-inducing peptide. [8]
Life extension is the concept of extending the human lifespan, either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled limit of 125 years. Several researchers in the area, along with "life extensionists", "immortalists", or "longevists", postulate that future breakthroughs in tissue rejuvenation, stem cells, regenerative medicine, molecular repair, gene therapy, pharmaceuticals, and organ replacement will eventually enable humans to have indefinite lifespans (agerasia) through complete rejuvenation to a healthy youthful condition. The ethical ramifications, if life extension becomes a possibility, are debated by bioethicists.
Melatonin is a natural compound, specifically an indoleamine, produced by and found in different organisms including bacteria and eukaryotes. It was discovered by Aaron B. Lerner and colleagues in 1958 as a substance of the pineal gland from cow that could induce skin lightening in common frogs. It was subsequently discovered as a hormone released in the brain at night which controls the sleep–wake cycle in vertebrates.
Carnosine (beta-alanyl-L-histidine) is a dipeptide molecule, made up of the amino acids beta-alanine and histidine. It is highly concentrated in muscle and brain tissues. Carnosine was discovered by Russian chemist Vladimir Gulevich.
Strategies for engineered negligible senescence (SENS) is a range of proposed regenerative medical therapies, either planned or currently in development, for the periodic repair of all age-related damage to human tissue. These therapies have the ultimate aim of maintaining a state of negligible senescence in patients and postponing age-associated disease. SENS was first defined by British biogerontologist Aubrey de Grey. Many mainstream scientists believe that it is a fringe theory.
Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars. They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney disease, and Alzheimer's disease.
Delta-sleep-inducing peptide (DSIP) is a neuropeptide that when infused into the mesodiencephalic ventricle of recipient rabbits induces spindle and delta EEG activity and reduced motor activities.
N-Acetylserotonin (NAS), also known as normelatonin, is a naturally occurring chemical intermediate in the endogenous production of melatonin from serotonin. It also has biological activity in its own right, including acting as a melatonin receptor agonist, an agonist of the TrkB, and having antioxidant effects.
Procollagen-proline dioxygenase, commonly known as prolyl hydroxylase, is a member of the class of enzymes known as alpha-ketoglutarate-dependent hydroxylases. These enzymes catalyze the incorporation of oxygen into organic substrates through a mechanism that requires alpha-Ketoglutaric acid, Fe2+, and ascorbate. This particular enzyme catalyzes the formation of (2S, 4R)-4-hydroxyproline, a compound that represents the most prevalent post-translational modification in the human proteome.
Nicotinamide phosphoribosyltransferase, formerly known as pre-B-cell colony-enhancing factor 1 (PBEF1) or visfatin for its extracellular form (eNAMPT), is an enzyme that in humans is encoded by the NAMPT gene. The intracellular form of this protein (iNAMPT) is the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD+) salvage pathway that converts nicotinamide to nicotinamide mononucleotide (NMN) which is responsible for most of the NAD+ formation in mammals. iNAMPT can also catalyze the synthesis of NMN from phosphoribosyl pyrophosphate (PRPP) when ATP is present. eNAMPT has been reported to be a cytokine (PBEF) that activates TLR4, that promotes B cell maturation, and that inhibits neutrophil apoptosis.
Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) is an enzyme that in humans is encoded by the nmnat1 gene. It is a member of the nicotinamide-nucleotide adenylyltransferases (NMNATs) which catalyze nicotinamide adenine dinucleotide (NAD) synthesis.
Sirtuin-activating compounds (STAC) are chemical compounds having an effect on sirtuins, a group of enzymes that use NAD+ to remove acetyl groups from proteins. They are caloric restriction mimetic compounds that may be helpful in treating various aging-related diseases.
Type 3 diabetes is a term proposed in 2016 to describe the interlinked association between type 1 and type 2 diabetes, and Alzheimer's disease. This term is used to look into potential triggers of Alzheimer's disease in people with diabetes. Use of the term dates back to at least 2008. However, the term was not officially accepted as of 2021 and it was not being used for diagnosis by most doctors.
Alex Zhavoronkov is a scientist and author working in biotechnology, regenerative medicine, and aging economics. He is the founder and CEO of Insilico Medicine, the director of the Biogerontology Research Foundation, a UK-based think-tank for aging research, and also the director of the International Aging Research Portfolio, an open-access repository of biomedical grants. He is an adjunct professor at the Moscow Institute of Physics and Technology.
Nicotinamide riboside (NR, SR647) is a pyridine-nucleoside and a form of vitamin B3. It functions as a precursor to nicotinamide adenine dinucleotide, or NAD+, through a two-step and a three-step pathway.
3-Indolepropionic acid (IPA), or indole-3-propionic acid, is a potent neuroprotective antioxidant, plant auxin, and natural product in humans that was being studied for therapeutic use in Alzheimer's disease as of 2002. It is endogenously produced by human microbiota and has only been detected in vivo when the species Clostridium sporogenes is present in the gastrointestinal tract. As of April 2016, C. sporogenes, which uses tryptophan to synthesize IPA, is the only species of bacteria known to synthesize IPA in vivo at levels which are subsequently detectable in the blood plasma of the host.
Nicotinamide mononucleotide is a nucleotide derived from ribose, nicotinamide, nicotinamide riboside and niacin. In humans, several enzymes use NMN to generate nicotinamide adenine dinucleotide (NADH). In mice, it has been proposed that NMN is absorbed via the small intestine within 10 minutes of oral uptake and converted to nicotinamide adenine dinucleotide (NAD+) through the Slc12a8 transporter. However, this observation has been challenged, and the matter remains unsettled.
Epitalon is a synthetic peptide, telomerase activator, and putative anti-aging compound, which was identified as the putative active component of a bovine pineal gland extract known as epithalamin.
Mitoquinone mesylate (MitoQ) is a synthetic analogue of coenzyme Q10 which has antioxidant effects. It was first developed in New Zealand in the late 1990s. It has significantly improved bioavailability and improved mitochondrial penetration compared to coenzyme Q10, and has shown potential in a number of medical indications, being widely sold as a dietary supplement.
Melatonin is a dietary supplement and medication as well as naturally occurring hormone. As a hormone, melatonin is released by the pineal gland and is involved in sleep–wake cycles. As a supplement, it is often used for the attempted short-term treatment of disrupted sleep patterns, such as from jet lag or shift work, and is typically taken orally. Evidence of its benefit for this use, however, is not strong. A 2017 review found that sleep onset occurred six minutes faster with use, but found no change in total time asleep.
Pinealon is a synthetic tripeptide of sequence (Glu-Asp-Arg) and purported geroprotector documented in the Russian scientific literature.
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