Aging And Disease

Aging is the lead risk factor for disease

Studies have shown the aging cell to be the leading risk factor for serious pathology. This is why it is our target to combat disease. Simply put, as cells age they become increasingly inept at functioning and repairing damage, leading to tissue and organ failure, and to disease.

Traditional medicine focuses on treating the symptoms of disease. BioViva focuses on the root cause. We are developing gene therapies that target cellular aging, and encourage cellular and tissue regeneration.

Among the various causes of aging, such as cellular senescence, accumulated waste, and changes to gene expression, are some of the leading risk factors of aging and disease. We are investigating a number of gene targets to help mitigate these forms of damage, and one of the most promising avenues of research is telomerase therapy.

The promise of telomerase therapy

Telomeres are repetitive DNA sequences located at the very ends of our chromosomes, which form a cap like structure that protects the cells from sensing the chromosome tips as ‘damaged’. The telomeres shorten with each cell division, and have been likened to the fuse on a stick of dynamite, steadily burning away until it has become too short. Then - depending on the type of cell- the cells enter either apoptosis (cell death), or replicative arrest known as senescence. It is believed that this cell division timer developed as a means to suppress tumours, and thus to prevent cells from becoming cancerous and replicating indefinitely. Studies have demonstrated that critically short telomeres present a barrier to prevent cancer (Artandi and DePinho, 2010).

However this tumour suppression mechanism comes at a cost. In the majority of our tissues telomeres grow shorter as we age, and ultimately contribute to the failure of organs and tissues. Data demonstrating how healthy life span correlates with longer telomeres in humans offer evidence for this. So does the observation that, the slower telomeres shorten, the slower the body succumbs to the consequences of aging . We also observe it in patients suffering from age related pathology, and from diseases that cause premature aging (Zhu et al, 2011).

Moreover it has been observed that cells with damaged and dysfunctional telomeres accumulate in the tissues of aging mice and primates. This supports the hypothesis that telomere attrition and cellular senescence promote aging (Fumagalli et al, 2012; Herbig et al, 2006, Hewitt et al, 2012). A number of researchers propose that the build up senescent cells, and the resulting toxic signals they send out, known as senescence-associated secretory phenotype, or SASP, is a cause of aging (Baker et al, 2011, Kirkland et al 2013).

Certain cells have the ability to stabilize telomere lengths more efficiently than others. Stem and progenitor cells can slow telomere erosion by the expression of a ribonucleoprotein complex called telomerase. Telomerase is able to preferentially lengthen telomeres that have become critically short, and are at the risk of becoming dysfunctional, by adding supplementary telomeric repeats to their concatenation. This allows the telomere to lengthen again, and thus prevents cell apoptosis or cell senescence. In contrast to stem cells, which are able to produce telomerase - to a lesser or greater degree depending on cell type - regular somatic cells, which make up most of the body, cease to express telomerase shortly before birth. As a result, in most of our cells telomeres shorten as we age, and while the low levels of telomerase expressed in stem cells are not enough to to totally prevent telomere erosion with age, it does slow down down aging significantly.

We observe that specially bred knock out mice, with a partially or fully reduced telomerase function, suffer from accelerated aging. We see similar results in humans, where loss of telomerase function leads to age related dysfunction and disease. Therefore the presence of active telomerase in stem cells is vital for longevity and health. Indeed, a recent study shows a direct correlation between living to a 100 and beyond, and having telomeres that loose length slowly. Scientists concluded that, whilst telomeres do not determine that a person will live to very old age, centenarians and their offspring maintain telomeres better than non-centenarians, and this improves their chances of living longer (Hirose, Zglinicki 2015). It is no surprise then that some researchers wonder if it is possible to slow down the aging process and increase healthy lifespan using telomerase delivered to our cells.

You can learn more about telomerase, the telomere theory of aging, and other aging theories here.