Although molecular features underlying aging and species maximum lifespan (MLS) have been comprehensively studied by transcriptome analyses, the actual impact of transcriptome on aging and MLS remains elusive. Here, we found that transcriptional signatures that are associated with mammalian MLS exhibited significant similarity to those of aging. Moreover, transcriptional signatures of longer MLS and aging both exhibited significant similarity to that of longer-lived mouse strains, suggesting that gene expression patterns associated with species MLS contribute to extended lifespan even within a species and that aging-related gene expression changes overall represent adaptations that extend lifespan rather than deterioration. Finally, we found evidence of co-evolution of MLS and promoter sequences of MLS-associated genes, highlighting the evolutionary contribution of specific transcription factor binding motifs such as that of E2F1 in shaping MLS-associated gene expression signature. Our results highlight the importance of focusing on adaptive aspects of aging transcriptome and demonstrate that cross-species genomics can be a powerful approach for understanding adaptive aging transcriptome.
© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.