Geroprotector

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A geroprotector 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]

Contents

Geroprotectors could belong to multiple classes depending on which of the hallmarks of aging they influence.

The distinction between geroprotectors and senotherapeutics is an evolving area of aging research. Geroprotectors broadly aim to target multiple mechanisms of aging, prolonging lifespan and healthspan by addressing the fundamental causes of aging. Senotherapeutics, on the other hand, are a subset of therapies that specifically target senescent cells, which are dysfunctional cells that accumulate with age and contribute to inflammation and age-related diseases. [9]

See also

Related Research Articles

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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 biological limit of around 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 through complete rejuvenation to a healthy youthful condition (agerasia). The ethical ramifications, if life extension becomes a possibility, are debated by bioethicists.

<span class="mw-page-title-main">Telomerase</span> Telomere-restoring protein active in the most rapidly dividing cells

Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most eukaryotes. Telomeres protect the end of the chromosome from DNA damage or from fusion with neighbouring chromosomes. The fruit fly Drosophila melanogaster lacks telomerase, but instead uses retrotransposons to maintain telomeres.

<span class="mw-page-title-main">Melatonin</span> Hormone released by the pineal gland

Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cows that could induce skin lightening in common frogs. This compound was later identified as a hormone secreted in the brain during the night, playing a crucial role in regulating the sleep-wake cycle, also known as the circadian rhythm, in vertebrates.

<span class="mw-page-title-main">Carnosine</span> Chemical compound

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. De Grey later highlighted similarities and differences of SENS to subsequent categorization systems of the biology of aging, such as the highly influential Hallmarks of Aging published in 2013.

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.

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

<span class="mw-page-title-main">Nicotinamide phosphoribosyltransferase</span> Human protein and coding gene

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.

The anti-aging movement is a social movement devoted to eliminating or reversing aging, or reducing the effects of it. A substantial portion of the attention of the movement is on the possibilities for life extension, but there is also interest in techniques such as cosmetic surgery which ameliorate the effects of aging rather than delay or defeat it.

<span class="mw-page-title-main">Type 3 diabetes</span> Medical condition

Type 3 diabetes is a proposed pathological linkage between Alzheimer's disease and certain features of type 1 and type 2 diabetes. Specifically, the term refers to a set of common biochemical and metabolic features seen in the brain in Alzheimer's disease, and in other tissues in diabetes; it may thus be considered a "brain-specific type of diabetes." It was recognized at least as early as 2005 that some features of brain function in Alzheimer's disease mimic those that underlie diabetes. However, the concept of type 3 diabetes is controversial, and as of 2021 it was not an officially recognized diagnosis.

<span class="mw-page-title-main">Nicotinamide riboside</span> Chemical compound

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.

A senolytic is among a class of small molecules under basic research to determine if they can selectively induce death of senescent cells and improve health in humans. A goal of this research is to discover or develop agents to delay, prevent, alleviate, or reverse age-related diseases. Removal of senescent cells with senolytics has been proposed as a method of enhancing immunity during aging.

Senotherapeutic's refers to therapeutic agents/strategies that specifically target cellular senescence. Senotherapeutic's include emerging senolytic/senoptotic small molecules that specifically induce cell death in senescent cells and agents that inhibit the pro-inflammatory senescent secretome. Senescent cells can be targeted for immune clearance, but an ageing immune system likely impairs senescent cell clearance leading to their accumulation. Therefore, agents which can enhance immune clearance of senescent cells can also be considered as senotherapeutic.

<span class="mw-page-title-main">Nicotinamide mononucleotide</span> Chemical compound

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.

Vadim N. Gladyshev is a professor of medicine at Brigham and Women's Hospital, Harvard Medical School, who specializes in antioxidant biology. He is known for his characterization of the human selenoproteome. He is also known for his work on the effects of aging in humans. He has conducted studies on whether organisms can acquire cellular damage from their food; the role selenium plays as a micro-nutrient with significant health benefits; In 2013 he won the NIH Pioneer Award.

<span class="mw-page-title-main">Epitalon</span> Synthetic peptide

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.

Senescence-associated secretory phenotype (SASP) is a phenotype associated with senescent cells wherein those cells secrete high levels of inflammatory cytokines, immune modulators, growth factors, and proteases. SASP may also consist of exosomes and ectosomes containing enzymes, microRNA, DNA fragments, chemokines, and other bioactive factors. Soluble urokinase plasminogen activator surface receptor is part of SASP, and has been used to identify senescent cells for senolytic therapy. Initially, SASP is immunosuppressive and profibrotic, but progresses to become proinflammatory and fibrolytic. SASP is the primary cause of the detrimental effects of senescent cells.

This timeline lists notable events in the history of research into senescence or biological aging, including the research and development of life extension methods, brain aging delay methods and rejuvenation.

<span class="mw-page-title-main">Mitoquinone mesylate</span> Chemical compound

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.

<span class="mw-page-title-main">Pinealon</span> Purported geroprotective agent

Pinealon is a synthetic tripeptide of sequence (Glu-Asp-Arg) and purported geroprotector documented in the Russian scientific literature.

References

  1. Alexey Moskalev, Elizaveta Chernyagina, Anna Kudryavtseva & Mikhail Shaposhnikov (2017). "Geroprotectors: A Unified Concept and Screening Approaches". Aging and Disease. 8 (3): 354–363. doi:10.14336/AD.2016.1022. PMC   5440114 . PMID   28580190.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. Alexey Moskalev, Elizaveta Chernyagina, João Pedro de Magalhães & Alex Zhavoronkov (2015). "Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease". Aging . 7 (9): 616–628. doi:10.18632/aging.100799. PMC   4600621 . PMID   26342919.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. Anisimov, VN; Popovich, IG; Zabezhinski, MA; Anisimov, SV; Vesnushkin, GM; Vinogradova, IA (2006). "Melatonin as antioxidant, geroprotector and anticarcinogen". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1757 (5–6): 573–89. doi: 10.1016/j.bbabio.2006.03.012 . PMID   16678784.
  4. Boldyrev, AA; Stvolinsky, SL; Fedorova, TN; Suslina, ZA (2010). "Carnosine as a natural antioxidant and geroprotector: From molecular mechanisms to clinical trials". Rejuvenation Research. 13 (2–3): 156–8. doi:10.1089/rej.2009.0923. PMID   20017611.
  5. Bulterijs, S (2011). "Metformin As a Geroprotector". Rejuvenation Research. 14 (5): 469–82. doi:10.1089/rej.2011.1153. PMID   21882902. S2CID   40645408.
  6. Dumas, Sabrina N; Lamming, Dudley W (2020-01-01). "Next Generation Strategies for Geroprotection via mTORC1 Inhibition". The Journals of Gerontology: Series A. 75 (1): 14–23. doi:10.1093/gerona/glz056. ISSN   1079-5006. PMC   6909887 . PMID   30794726.
  7. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice, Cell Metabolism 24, 795–806, December 13, 2016 ª 2016 Elsevier Inc.
  8. Bondarenko, TI (2011). "Mechanism of delta-sleep inducing peptide geroprotective activity". Adv Gerontol. 24 (1): 80–92. PMID   21809625.
  9. Al-Naggar, Iman M. A. (24 October 2020). "Senolytics: Targeting Senescent Cells for Age-Associated Diseases". Current Molecular Biology Reports. 6: 161–172 via Springer.