Title : Decoding the secret of longevity through big data: Noncoding RNAs—not proteins—drive animal lifespan evolution
Abstract:
The mechanisms governing lifespan evolution across organisms have long remained elusive. Integrative analyses of multiple large-scale datasets across the animal kingdom now reveal that noncoding RNAs (ncRNAs), rather than proteins, serve as the principal drivers of lifespan evolution. Evolutionary expansion of genomic ncRNA length coincides with coordinated reduction of mitochondrial genome size, establishing a highly efficient energy-utilization model associated with extended longevity. As species evolve longer lifespans, they consistently acquire longevity-enhancing ncRNA motifs while selectively eliminating short-lived ones forming a dynamic and progressive evolutionary pattern distinct from the relatively conserved trajectory of protein evolution. Longevity- associated ncRNA motifs, such as GGTGCG, are highly enriched and actively expressed in critical tissues including the endometrium, ovaries, testes, and cerebral cortex. Notably, the ovary and endometrium harbor a greater abundance of activating ncRNAs than the testis, providing a compelling molecular explanation for the well-established observation that women generally outlive men. Collectively, these findings establish ncRNAs as central evolutionary architects of two defining biological traits longevity and reproduction demonstrating that their functional capacity far surpasses conventional assumptions. This discovery provides a transformative conceptual framework for advancing aging research and developing innovative strategies to promote healthy lifespan extension.
