A gene sequence is made up of a combination of shorter sequences, some of which are used to create the protein encoded in that gene. These shorter sequences include exons and exclude introns. However, changes in which exons and introns are used in protein production can result in multiple proteins being produced from a single gene sequence. This can happen accidentally, leading to the production of toxic proteins. Alternatively, it can be an evolutionary process where a gene produces different vital proteins with distinct functions.
The process of interpreting a gene sequence to produce messenger RNA (mRNA) molecules for a specific protein, through the inclusion of some or all exons and exclusion of introns, is known as RNA splicing. When a different protein is produced instead of the dominant one, it is referred to as alternative splicing. This is a complex process that can be impacted by changes in gene expression and other forms of cell damage, potentially leading to the production of malformed, toxic proteins.
The role of alternative splicing in the complex web of aging-related processes is still not fully understood. However, research suggests that methods of slowing aging are associated with less disruption of RNA splicing. Some groups are working on restoring youthful organization of RNA splicing, and initial results are promising. It remains to be seen how this research will progress given the relatively early stage of this area of study and development.
The article “Age-Related Alternative Splicing: Driver or Passenger in the Aging Process?” discusses the link between alternative splicing and aging, highlighting that changes in splicing may accelerate aging and age-related disorders. In higher eukaryotic genomes, alternative splicing contributes to increasing the functional diversity and complexity of the transcriptome and appears to be a master regulator of cellular and individual aging.
The piece delves into the different tissues and organs that may experience age-related alterations in transcriptional and post-transcriptional regulation, and how splicing errors during pre-mRNA processing can contribute to aging-dependent splicing alterations. It also emphasizes the importance of further understanding how RNA splicing is impacted by aging to establish its role in driving aging and its implications for increasing the healthy human lifespan.
