Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats

Anisimov, Vladimir N.; Mylnikov, S. V.; Khavinson, V. Kh.

doi:10.1016/s0047-6374(98)00034-7

Cited by 37 publications

(8 citation statements)

References 31 publications

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“…Changes in GSH levels with aging are controversial [48,49]. Several experiments have indicated that supplementation of melatonin to aging rodents may retard some processes of senescence [50,51]. (6) The physiological concentrations of tissue melatonin in vertebrates may be in nM range, an estimate based on the plasma melatonin concentrations.…”

Section: Melatoninmentioning

confidence: 99%

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

et al. 2000

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Melatonin is a potent endogenous free radical scavenger, actions that are independent of its many receptor-mediated effects. In the last several years, hundreds of publications have confirmed that melatonin is a broad-spectrum antioxidant. Melatonin has been reported to scavenge hydrogen peroxide (H₂O₂), hydroxyl radical (HO·), nitric oxide (NO·), peroxynitrite anion (ONOO^–), hypochlorous acid (HOCl), singlet oxygen (¹O₂), superoxide anion (O₂^–·) and peroxyl radical (LOO·), although the validity of its ability to scavenge O₂^–· and LOO· is debatable. Regardless of the radicals scavenged, melatonin prevents oxidative damage at the level of cells, tissues, organs and organisms. The antioxidative mechanisms of melatonin seem different from classical antioxidants such as vitamin C, vitamin E and glutathione. As electron donors, classical antioxidants undergo redox cycling; thus, they have the potential to promote oxidation as well as prevent it. Melatonin, as an electron-rich molecule, may interact with free radicals via an additive reaction to form several stable end-products which are excreted in the urine. Melatonin does not undergo redox cycling and, thus, does not promote oxidation as shown under a variety of experimental conditions. From this point of view, melatonin can be considered a suicidal or terminal antioxidant which distinguishes it from the opportunistic antioxidants. Interestingly, the ability of melatonin to scavenge free radicals is not in a ratio of mole to mole. Indeed, one melatonin molecule scavenges two HO·. Also, its secondary and tertiary metabolites, for example, N¹-acetyl-N²-formyl-5-methoxykynuramine, N-acetyl-5-methoxykynuramine and 6-hydroxymelatonin, which are believed to be generated when melatonin interacts with free radicals, are also regarded as effective free radical scavengers. The continuous free radical scavenging potential of the original molecule (melatonin) and its metabolites may be defined as a scavenging cascade reaction. Melatonin also synergizes with vitamin C, vitamin E and glutathione in the scavenging of free radicals. Melatonin has been detected in vegetables, fruits and a variety of herbs. In some plants, especially in flowers and seeds (the reproductive organs which are most vulnerable to oxidative insults), melatonin concentrations are several orders of magnitude higher than measured in the blood of vertebrates. Melatonin in plants not only provides an alternative exogenous source of melatonin for herbivores but also suggests that melatonin may be an important antioxidant in plants which protects them from a hostile environment that includes extreme heat, cold and pollution, all of which generate free radicals.

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Section: Melatoninmentioning

confidence: 99%

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

et al. 2000

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“…Melatonin is secreted by the pineal gland and several other tissues, including the gastrointestinal tract, in a pulsatile pattern peaking in the early morning (Klein et al, 1992). Melatonin has been reported to improve sleep, increase longevity, lower blood pressure, strengthen the immune system, and act as an antioxidant (Chase and Gidal, 1997;Skene et al, 1999;Anisimov et al, 1998;Nishiyama et al, 2001;Reiter, 1995). With advancing age the pineal gland shrinks and melatonin secretion decreases and may be accompanied by a shift in the phase of its pulsatile release (Nishiyama et al, 2001;Kripke et al, 1998).…”

Section: Biomarkersmentioning

confidence: 99%

Calorie restriction in rhesus monkeys

Mattison¹

2003

Experimental Gerontology

235

161

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Calorie restriction (CR) extends lifespan and reduces the incidence and age of onset of age-related disease in several animal models. To determine if this nutritional intervention has similar actions in a long-lived primate species, the National Institute on Aging (NIA) initiated a study in 1987 to investigate the effects of a 30% CR in male and female rhesus macaques (Macaca mulatta) of a broad age range. We have observed physiological effects of CR that parallel rodent studies and may be predictive of an increased lifespan. Specifically, results from the NIA study have demonstrated that CR decreases body weight and fat mass, improves glucoregulatory function, decreases blood pressure and blood lipids, and decreases body temperature. Juvenile males exhibited delayed skeletal and sexual maturation. Adult bone mass was not affected by CR in females nor were several reproductive hormones or menstrual cycling. CR attenuated the age-associated decline in both dehydroepiandrosterone (DHEA) and melatonin in males. Although 81% of the monkeys in the study are still alive, preliminary evidence suggests that CR will have beneficial effects on morbidity and mortality. We are now preparing a battery of measures to provide a thorough and relevant analysis of the effectiveness of CR at delaying the onset of age-related disease and maintaining function later into life.

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“…Clearly, a very "minute" amount of PAK1 is sufficient for controlling the inducible melanogenesis by a robust phosphorylation of PAK1 at to be PAK1-dependent [6]. Most interestingly, it was found by Georges Maestroni's team in Switzerland around 1985 to be a powerful elixir that extends the healthy lifespan of 19-months-old mice by 20% as well as Drosophila and rats [10]. To the best of our knowledge, melatonin is the very first among natural or synthetic compounds to be identified as a "real" elixir (longevity-promoter or anti-ageing drug).…”

Section: Check For Updatesmentioning

confidence: 99%

Natural or Synthetic Anti-Melanogenic Compounds That Block the PDGFR-EGFR-PAK1-MITF-Tyrosinase Signaling Pathway

Miyata¹,

Pham-Thi²,

Ahn³

2017

J Dermatol Res Ther

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A natural sleeping pill and "elixir" (longevity-promoter) called "Melatonin" is one of the first natural anti-melanogenic compounds, and originally derived from bovine pineal glands. However, currently the majority of melatonin product in the market is chemically synthesized. Since then a wide variety of anti-melanogenic compounds such as curcumin, CAPE (Caffeic Acid Phenethyl Ester), and Artepillin C (ARC) were identified in nature as well as chemically synthesized compounds such as Gleevec. These anti-melanogenic compounds share a series of interesting biological properties such as anti-cancer, anti-inflammatory, anti-ageing (longevity-promoting), immune-boosting, anti-malaria, and anti-diabetic activities. However, the precise molecular mechanism underlying their anti-melanogenic action has remained to be clarified until recently. Finally we found the first clue to understanding of the "melanogenic" signalling pathway involving the major oncogenic/ageing kinase called PAK1 (RAC/CDC42-activated kinase 1) By siRNA-based silencing of PAK1 gene in murine melanoma cell line (B16F10): (i) The major growth hormone in serum called PDGF (Platelet-Derived Growth Factor) is essential for the inducible melanogenesis, but not for the exponential growth per se, and (ii) This cytokine activates its receptor called PDGFR, a Tyr-kinase on the cell surface, and induces another cell surface receptor Tyr-kinase called EGFR (Epidermal Growth Factor Receptor), to form a heterodimer with PDGFR, activating the down-stream melanogenic/oncogenic signalling pathway involving PAK1 and eventually MITF (Microphthalmia-Associated Transcription Factor) essential for expression of Tyrosinase and its Related Protein (TRP) genes. Melatonin and many other anti-melanogenic compounds block PAK1 directly or indirectly, and eventually down-regulate tyrosinase or TRP which is essential for melanin biosynthesis from an amino acid called tyrosine.

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Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats

Cited by 37 publications

References 31 publications

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

Calorie restriction in rhesus monkeys

Natural or Synthetic Anti-Melanogenic Compounds That Block the PDGFR-EGFR-PAK1-MITF-Tyrosinase Signaling Pathway

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