Evolutionary transcriptomics reveals longevity mostly driven by polygenic and indirect selection in mammals

Abstract

The maximum lifespan varies more than 100-fold in mammals. This experiment of nature may uncover of the evolutionary forces and molecular features that define longevity. To understand the relationship between gene expression variation and maximum lifespan, we carried out a comparative transcriptomics analysis of liver, kidney, and brain tissues of 106 mammalian species. We found that expression is largely conserved and very limited genes exhibit common expression patterns with longevity in all the three organs analyzed. However, many pathways, e.g., Insulin signaling pathway, and FoxO signaling pathway, show accumulated correlations with maximum lifespan across mammals. Analyses of selection features further reveal that methionine restriction related genes whose expressions associated with longevity, are under strong selection in long-lived mammals, suggesting that a common approach could be utilized by natural selection and artificial intervention to control lifespan. These results suggest that natural lifespan regulation via gene expression is likely to be driven through polygenic model and indirect selection.

Comparative susceptibility of SARS-CoV-2, SARS-CoV, and MERS-CoV across mammals

“…To generate the species-specific ortholog sets and calculate expression values, we downloaded the reference genomes of species (if available) from the public database. For those without a reference genome, Trinity was used to perform de novo assembly of transcripts [37] based on previously generated liver, kidney, and brain transcriptome to assemble transcripts [38]. The fixed parameter k-mer size was 25, the minimum contig length was 200, and the paired fragment length was 500.…”

Evolutionary paths to mammalian longevity through the lens of gene expression

“…The natural variation in mammalian longevity and its underlying mechanisms remain an active area of aging research. In the latest issue of The EMBO Journal, Liu et al (2023) analyze gene expression levels in 103 mammalian species across three tissues, revealing tissue-specific associations between gene expression patterns and longevity. Remarkably, the study suggests that methionine restriction, a strategy shown to increase lifespan, may extend beyond artificial interventions and is similarly employed by natural selection.…”

“…This highlights a shared strategy between natural selection and human-induced laboratory interventions, such as drug treatments or genetic manipulations, aimed at anti-aging and the regulation of lifespan. Liu et al (2023) present a combination of extensive data collection and an innovative approach to comparative genomics of aging by merging genomics and transcriptomics. Through the integration of diverse data from multiple species, they have laid a strong foundation for future studies.…”

“…Figure1. Graphical overview of the workflow adopted byLiu et al (2023). Integration of a comprehensive dataset from liver, kidney, and brain tissues of 103 mammal species with maximum lifespans ranging from about 3 years to over 200 years (left panel).…”