Abstract
During human ageing there is an increase in the activity of inflammatory, cancer-promoting, and tissue destructive genes plus a decrease in the activity of regenerative and reparative genes. The human blood tripeptide GHK possesses many positive effects but declines with age. It improves wound healing and tissue regeneration (skin, hair follicles, stomach and intestinal linings, and boney tissue), increases collagen and glycosaminoglycans, stimulates synthesis of decorin, increases angiogenesis, and nerve outgrowth, possesses antioxidant and anti-inflammatory effects, and increases cellular stemness and the secretion of trophic factors by mesenchymal stem cells. Recently, GHK has been found to reset genes of diseased cells from patients with cancer or COPD to a more healthy state. Cancer cells reset their programmed cell death system while COPD patients’ cells shut down tissue destructive genes and stimulate repair and remodelling activities. In this paper, we discuss GHK’s effect on genes that suppress fibrinogen synthesis, the insulin/insulin-like system, and cancer growth plus activation of genes that increase the ubiquitin-proteasome system, DNA repair, antioxidant systems, and healing by the TGF beta superfamily. A variety of methods and dosages to effectively use GHK to reset genes to a healthier state are also discussed.
According to the Administration on Aging (http://www.aoa.gov/), there were 39 million people aged 65 and older in 2009 which constituted 12% of the American population. By 2030 it is expected that 19% of the population will be over 65. With life expectancy continuing to increase, we may expect that this trend is here to stay. Unfortunately, with advanced age comes not only wisdom but also many age-related pathological conditions that account for the high rates of hospitalization, increased cost of health care and decreased quality of life. Today, more than ever, there is an urgent need to find safe, easy-to-administer, cost-effective methods, which could not only delay the onset of the age related diseases, but also restore health.
It now becomes increasingly clear that the primary cause of human aging and its attendant diseases is changes in the activity of the human genome. During aging there is an increase in the activity of inflammatory, cancer promoting, and tissue destructive genes plus a decrease in the activity of regenerative and reparative genes [1].
The most exciting discovery of the past decades is that these changes in gene activity can be reversed, often by quite simple and natural molecules [2]. Recent discoveries on the actions of the human tripeptide GHK (glycyl-L-histidyl-L-lysine) to reset gene expression of human cells to a more healthy state may open a door to the therapeutic resetting of genes in the elderly. This can be useful as a preventative measure and a complimentary treatment for conditions typically associated with aging such as cancer, Alzheimer’s, chronic obstructive lung disease (COPD), nephropathy, and retinopathy.
GHK was discovered during studies comparing the effect of human plasma from young persons (age 20–25) to plasma from older persons (age 50–70) on the functioning of incubated slices of human hepatic tissue. The younger plasma more effectively induced a profile associated with youth by suppressing fibrinogen synthesis. The active factor was found to be GHK. Since then numerous studies over the course of four decades demonstrated that this simple molecule improves wound healing and tissue regeneration (skin, hair follicles, bones, stomach, intestinal linings, and liver), increases collagen and glycosaminoglycans, stimulates synthesis of decorin, increases angiogenesis, and nerve outgrowth; possesses antioxidant and anti-inflammatory effects, and increases cellular stemness and the secretion of trophic factors by mesenchymal stem cells [3–6].
GHK’s actions on gene expression were determined by the Broad Institute and, using their data, we determined that GHK increased or decreased gene expression (UP or DOWN more than 50%) in 32.1% of the human genes [7]. In a recent gene study, the Broad Institute’s Connectivity Map was used to find potential therapeutic agents for aggressive, metastatic colon cancer [8]. The gene analysis computer program selected GHK from 1,309 bioactive molecules as the best choice to reset the diseased gene patterns to a healthier pattern. When three lines of human cancer cells (SH-SY5Y neuroblastoma cells, U937 histolytic cells, breast cancer cells) were incubated in culture with 1 to 10 nanomolar GHK, the programmed cell death system (apoptosis) was reactivated and cell growth inhibited [9]. When cells derived from the damaged areas of the lungs of COPD patients were incubated with 10 nanomolar GHK, the tripeptide recapitulated TGF beta induced genes expression patterns which led to the organization of the actin cytoskeleton and elevated the expression of integrin. This restored proper collagen contraction and remodeling by lung fibroblasts [10]. These results, combined with GHK’s broad spectrum of positive actions on many systems that maintain human health, suggest that therapies using GHK might provide health benefits to the elderly.
In this paper, we discuss the following actions of GHK on genes important in healthy aging.
