Livagen

In peripheral lymphocytes from elderly donors, Livagen (Lys-Glu-Asp-Ala) was assessed for effects on ribosomal (NOR) gene activity, heterochromatin melting/denaturation parameters, structural C-heterochromatin polymorphism, and facultative heterochromatin variability. Livagen induced activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin, and de-repression of genes silenced by age-related euchromatin condensation. The authors interpreted this as chromatin reactivation via modification of heterochromatinized chromosomal regions.

Scientists tested Livagen on immune cells taken from old people. As we age, parts of our DNA get tightly packed away and switched off; Livagen appeared to loosen this packing and switch some of those genes back on. The finding suggests the peptide can partially reverse age-related silencing of genes in these cells, at least in the lab. It is early Khavinson-group research.

Using in vitro assays with tritiated leucine-enkephalin, Livagen (Lys-Glu-Asp-Ala) and Epitalon (Ala-Glu-Asp-Gly) were tested for inhibition of enkephalin-degrading enzymes in human serum and for binding to brain opioid receptors. Both peptides inhibited enkephalin-degrading enzymes, with Livagen more potent (IC50 approximately 20 microM versus 500 microM for Epitalon), exceeding some reference peptidase inhibitors. Radioreceptor assays showed no direct binding of either peptide to mu- or delta-opioid receptors in rat brain membranes.

This lab study looked at whether Livagen affects the body's natural painkiller (enkephalin) system. Livagen slowed the enzymes that break down enkephalins, and did so more strongly than the comparison peptide, which could in theory prolong enkephalin activity. However, Livagen did not directly attach to opioid receptors, so any effect would be indirect.

Livagen (Lys-Glu-Asp-Ala) was shown to be resistant to hydrolysis by small-intestinal peptidases, and in vitro it reduced glycyl-L-leucine dipeptidase activity by about 50%. After two weeks of oral administration in rats, digestive-enzyme activity shifted in an age-dependent manner: decreasing in young animals but increasing in old animals. In aged rats, enzyme activity after Livagen in most cases approached the levels seen in untreated young control animals.

Rats of different ages were given Livagen by mouth for two weeks, and their gut digestive enzymes were measured. Livagen nudged the enzyme levels of old rats back toward those of young rats, acting as an age-normalizing regulator rather than simply raising or lowering activity. The peptide also resisted being digested itself, which may help it reach the gut intact.