TELOMERASE: the enzyme that turns back the hands of time

Telomerase

Telomeres are DNA and protein structures at the ends of chromosomes, consisting of small tandemly repeated nucleotide sequences (5′-TTAGGG-3′ in humans). Their importance lies in their ability to provide DNA stability, preventing chromosomes from wrapping around themselves or recombining at their ends, leading to cell death.

The telomere plays a crucial role in preventing the loss of information during chromosome duplication, as DNA polymerase is unable to replicate the chromosome to its termination. With each DNA duplication and subsequent cell division, telomeres become progressively shorter, but their original length is restored by an important enzyme called telomerase.

Senescence

This enzyme is not always active. In humans, telomerase is only active during embryonic development, in stem cells and in the adult germ line. It is estimated that telomeres shorten by 50 to 200 base pairs with each replicative cycle.

When a minimum critical telomere length is reached, cellular signals are triggered that cause cells to enter replicative senescence, i.e. a phase in which cell proliferation is permanently halted. Senescent cells remain metabolically active, but their gene expression is altered and consequently their division cycles slow down.

Studies and research

Several studies have been carried out to highlight the correlation between telomerase activity and ageing. To this end, the telomere length of chromosomes from cells of individuals aged between 0 and 93 years was modified in the laboratory (using nucleases). The results of these experiments showed an obvious relationship between proliferative activity and age.

Proliferation is normally greater in the cells of young individuals, but what was surprising was the demonstration of a correlation between replicative capacity and telomere length across the entire age range of the subjects. This indicated that cells with shortened telomeres experimentally replicated less than those with longer telomeres.

These observations support the hypothesis that telomere length is a biomarker for the aging of human somatic cells. As they shorten with each cell division, telomeres act like molecular clocks, indicating the number of times the cell has split.

SIRT1 and telomerase

Today, many research laboratories are looking for ways to reset the biological clock in order to elongate chromosome ends in eukaryotic cells and thus slow down the aging process. In this context, many studies show that the expression of SIRT1 can preserve the integrity of the genome and its stability.

Among these, one in particular has demonstrated how SIRT1 can impact telomere length maintenance by analysing both loss of SIRT1 function and increase in function using mice with SIRT1 over-expression. SIRT1 over-expression in mice leads to a decrease in the rate of telomere erosion associated with cell division and tissue ageing, while SIRT1 deletion leads to the opposite effect.

The beneficial effects of SIRT1 on telomere length occur without any negative effects on telomere integrity. These results have been confirmed by other studies, which also show the beneficial effects of SIRT1 on telomerase activity and the response to DNA damage.

But how can we increase or restore sirtuin production in humans and thus reactivate telomerase? Through the consumption of polyphenols.