Vilon

What it is. Vilon is Lys-Glu, a dipeptide - two amino acids. It was designed from the amino acid composition of thymic extract in the same way Epitalon was designed from pineal extract, and it is one of the components later identified inside Thymalin [5]. Being a dipeptide makes it the simplest compound on this site by some margin.

The mouse data, which are the best in this group. Subcutaneous vilon given to female CBA mice from the sixth month of life increased physical activity and endurance, decreased body temperature, prolonged lifespan and prevented the development of spontaneous neoplasms. Long-term administration caused no unfavourable effects on development, and the authors concluded chronic administration was safe [1]. A companion paper reported inhibition of spontaneous tumour growth and increased lifespan [2], and a later study examined effects in dimethylhydrazine-induced neoplasia [6].

Note what the same paper reports as not changing: age-related changes in oestrous function, and free radical processes [1]. A study that reports its null results alongside its positive ones is more credible than one that does not, and this is worth crediting.

The microarray result. Expression of 15,247 clones was measured in mouse heart. Vilon changed 36 of them by more than two-fold; epitalon changed 98; the combination changed 144 [3]. This is the most concrete mechanistic data in the whole Khavinson programme, and it points in a specific direction: these are modest, selective effects on a small number of genes, not a global reprogramming. That is more plausible biology than the marketing suggests, and a lower ceiling on what to expect.

The human work. Lymphocytes from donors aged 75-88 were treated in culture. Vilon activated ribosomal genes and induced deheterochromatinisation of total heterochromatin - but unlike epitalon and livagen, it did not decondense pericentromeric structural heterochromatin on chromosomes 1 and 9 [4]. These are cells in a dish from human donors, not people taking a drug.

What does not exist. A clinical trial of vilon. Pharmacokinetics in any species. Anything beyond the programme that developed it.

The proposed mechanism is the one shared across this family: a peptide small enough to enter the cell and the nucleus, binding DNA or chromatin and altering transcription [7][8]. For vilon specifically, the microarray work gives that claim actual numbers - 36 of 15,247 clones changed more than two-fold in mouse heart [3] - and the chromatin studies describe decondensation of heterochromatin in aged lymphocytes [4][9]. The programme has also proposed ageing markers such as CCL11 and HMGB1 as readouts for these peptides [10].

The differences between peptides in that chromatin work are the most interesting detail. Epitalon and livagen decondense pericentromeric heterochromatin; vilon does not [4]. If these peptides were acting non-specifically - as charged small molecules perturbing chromatin - they would behave alike. They do not, which supports sequence-specific interaction, and is consistent with the DNA-binding study that found different peptides prefer different nucleotide motifs [7].

The gap remains what it is for the whole programme: an effect demonstrated on cells in a dish and on gene expression in a dosed mouse, with no measurement of whether an injected or swallowed dipeptide survives long enough to reach a cell nucleus in a person.

The free dipeptide Lys-Glu, supplied lyophilised. Animal work used subcutaneous and intramuscular injection; oral products are sold in Russia without a published absorption study.

It is one of the dipeptides since identified within Thymalin, the thymic extract from which it was originally designed [5].

The mouse evidence is genuinely reassuring as far as it goes: long-term administration from mid-life to death caused no unfavourable effects on development, and the authors explicitly concluded that chronic administration is safe and the preparation suitable for geroprotection [1].

That is a statement about mice. There is no human safety data, no pharmacokinetics in any species, and no post-marketing surveillance available in English.

One point in vilon's favour relative to the rest of this group: the tumour data run in the protective direction - it inhibited spontaneous tumour growth [1][2] - rather than raising the questions that Epitalon's telomerase activation does.

The usual caveats about provenance apply. Almost the entire literature comes from the St Petersburg institute and its collaborators, much of it in Bulletin of Experimental Biology and Medicine, and none of the key results has been independently replicated.

The combination studied is with Epitalon: given together in mouse heart, the two peptides changed expression of 144 clones against 36 for vilon alone and 98 for epitalon alone - more than either but less than the sum, suggesting overlapping targets [3]. They were also studied together for effects on intestinal enzyme activity in old rats [11].

No adverse interaction has been reported, and no combination has been studied in humans.