When genes are switched on, they make a message (mRNA), containing the instructions to make whatever the cell requires. Most genes can make more than one type of mRNA message (mRNA isoform), depending on the needs of the cell in a process termed ‘alternative splicing’. The balance of mRNA isoforms made from each gene is critical and underpins the ability of cells to adapt and respond to their environment. This ability to ‘fine tune’ gene outputs is vital for long-term health. The choice of which isoforms are produced is made by a set of regulatory proteins (collectively termed splicing factors).
Our founders have discovered that levels of splicing factors change during ageing, compromising our ability to carry out this ‘fine tuning’ of gene expression. This is a fundamental reason why cells become senescent. Compromised molecular resilience is a major cause of the ill health and frailty that accompanies ageing. We have demonstrated that restoration of splicing factor levels to those seen in younger cells is able to effectively turn back the ageing clock in old cells, bringing about reversal of senescence.
At SENISCA, we are using oligonucleotide-based therapeutic approaches to reset splicing factor levels and reverse senescence. We anticipate that understanding the molecular basis of rejuvenation will highlight new treatments for the diseases and aesthetic aspects of ageing. More importantly, it is likely that preventative approaches based on rejuvenation will be developed reducing both disease incidence and severity.