2014年4月23日星期三

Epitalon Research Article – Part 1

Epitalon Research Article – Part 1

Today we are presenting to you Part 1 Epitalon research article.
Title: Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice
Part 1 - Introduction
The search for new effective and safe means to prevent premature aging is one of the priorities in gerontology (Anisimov 2001; Butler et al. 2002; De Grey et al. 2002). During the last decade a number of reports have appeared on the role of the pineal gland in aging (Armstrong and Redman 1991; Reiter 1995; Reppert and Weaver 1995; Pierpaoli 1998; Reiter et al. 2002).
Pineal Gland
Pineal Gland
A modulating effect of the pineal gland on theneuroendocrine and the immune system was shown to change during aging (Arendt 1995). Pinealectomized rats showed a reduced life span (Malm et al. 1956; Reiter et al. 1999), whereas the administration of the pineal hormonemelatonin to rodents or syngeneic transplantation of pineal glands from young donors into the thymus orin situof old mice prolonged the life span of the recipients (Pierpaoli and Regelson 1994; Lesnikov and Pierpaoli 1994; Anisimov et al. 2001b; Oxenkrug et al. 2001).
Most investigators invoked melatonin as a primary mediator of the endocrine capabilities of the pineal gland. However, some of the effects of the pineal gland might have obviously resulted from pineal peptide secretion (Benson 1977; Bartsch et al. 1992; Yuwiler and Brammer 1993; Arendt 1995). Some crude peptide extracts or purified peptides isolated from pineal glands were
shown to have antigonadotropic, metabolic and anti-194 tumor activity (Anisimov et al. 1994; Bartsch et al. 1992; Lapin and Ebels 1979).
One of the complex peptide bioregulators isolated from the pineal gland, Epithalamin , was shown to slow down aging rate, prolong life span in fruit flies, mice and rats, and inhibit spontaneous and induced carcinogenesis in rodents (Anisimov et al. 1994; Khavinson et al. 2001c; Khavinson 2002). Tetrapeptide Epitalon (Ala-Glu-Asp-Gly, molecular weight 390.35 dalton) was designed on the basis of Epithalamin amino acid analysis and synthesized (Khavinson et al. 2000).
The geroprotective activity of Epitalon was studied in three strains of Drosophila melanogaster(Khavinson et al. 2000; Mylnikov and Lyubimova 2000). Epitalon increased the life span of imagoes significantly by 11–16% when applied at unprecedentedly low concentrations – from 0.001×10 −6 to 5 ×10 −6 wt% of the culture medium. A recent study by us demonstrated a geroprotective effect of long-term Epitalon administration in female inbred CBA mice (Anisimov et al. 2001a).
The bioregulator slowed down aging of the reproductive function, inhibited free radical processes, and decreased total spontaneous tumor incidence in female CBA mice (Anisimov et al. 2001a). Epitalon inhibited mammary carcinogenesis and metastasis in transgenic HER-2/neumice (Anisimov et al. 2002b) and colon and small intestine carcinogenesis induced by 1,2-dimethylhydrazine in rats (Anisimov et al. 2002a).
Administration of Epitalon to young (6–8 years old) and senescent (20–26 years old) female monkeysMacaca mulattarestored the evening level of melatonin and the circadian rhythm of cortisol in the blood serum of senescent monkeys (Khavinson et al. 2001a).
This paper presents data on the effect of Epitalon on life span, estrous function, incidence of chromosome aberration in the bone marrow cells and spontaneous tumorigenesis in outbred Swiss-derived SHR mice.

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