Transcript diversity in aging: cryptic transcription and splicing

Increased transcript diversity, which is caused in part by alternative splicing and cryptic transcription, is an underappreciated aspect of age-associated transcriptome remodeling. Recent work has revealed that structurally novel transcripts increase during aging in many tissues. Genes with cryptic and alternatively spliced transcripts with age are enriched for functional categories relevant to tissue function and aging, and have been implicated in cognitive decline, decreased muscle strength, reduced oocyte quality, immune aging, altered stem cell properties, and senescence. Indeed, there is emerging evidence that alternatively spliced transcripts and elevated cryptic transcription directly contribute to aging phenotypes in multiple tissues. The full impact of the increased transcript diversity on the aging process has yet to be explored. The increased transcript diversity engendered by alternative splicing and cryptic transcription is emerging as a potent driver of aging and aging phenotypes, adding another layer to our understanding of the transcriptional regulation of aging.