Katari, M. S. | bioRxiv Science

bioRxiv2025

SkeletAge: Transcriptomics-based Aging Clock Identifies 26 New Targets in Skeletal Muscle Aging

Identifying the set of genes that regulate baseline healthy aging - aging that is not confounded by illness - is critical to understating aging biology. Machine learning-based age-estimators (such as epigenetic clocks) offer a robust method for capturing biomarkers that strongly correlate with age. In principle, we can use these estimators to find novel targets for aging research, which can then be used for developing drugs that can extend the healthspan. However, methylation-based clocks do not provide direct mechanistic insight into aging, limiting their utility for drug discovery. Here, we describe a method for building tissue-specific bulk RNA-seq-based age-estimators that can be used to identify the ageprint. The ageprint is a set of genes that drive baseline healthy aging in a tissue-specific, developmentally-linked fashion. Using our age estimator, SkeletAge, we narrowed down the ageprint of human skeletal muscles to 128 genes, of which 26 genes have never been studied in the context of aging or aging-associated phenotypes. The ageprint of skeletal muscles can be linked to known phenotypes of skeletal muscle aging and development, which further supports our hypothesis that the ageprint genes drive (healthy) aging along the growth-development-aging axis, which is separate from (biological) aging that takes place due to illness or stochastic damage. Lastly, we show that using our method, we can find druggable targets for aging research and use the ageprint to accurately assess the effect of therapeutic interventions, which can further accelerate the discovery of longevity-enhancing drugs.

bioinformatics↗

bioRxiv2023

The genome of the Wollemi pine, a critically endangered living fossil unchanged since the Cretaceous, reveals extensive ancient transposon activity.

We present the genome of the living fossil, Wollemia nobilis, a southern hemisphere conifer morphologically unchanged since the Cretaceous. Presumed extinct until rediscovery in 1994, the Wollemi pine is critically endangered with less than 60 wild adults threatened by intensifying bushfires in the Blue Mountains of Australia. The 12 Gb genome is among the most contiguous large plant genomes assembled, with extremely low heterozygosity and unusual abundance of DNA transposons. Reduced representation and genome re-sequencing of individuals confirms a relictual population since the last major glacial/drying period in Australia, 120 ky BP. Small RNA and methylome sequencing reveal conservation of ancient silencing mechanisms despite the presence of thousands of active and abundant transposons, including some transferred horizontally to conifers from arthropods in the Jurassic. A retrotransposon burst 8-6 my BP coincided with population decline, possibly as an adaptation enhancing epigenetic diversity. Wollemia, like other conifers, is susceptible to Phytophthora, and a suite of defense genes, similar to those in loblolly pine, are targeted for silencing by sRNAs in leaves. The genome provides insight into the earliest seed plants, while enabling conservation efforts.

genomics↗