bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/207647

Universal transcriptomic signature of age reveals temporal scaling of Caenorhabditis elegans aging trajectories

Tarkhov, A. E.·Alla, R.·Ayyadevara, S.·Pyatnitskiy, M.·Menshikov, L.·Shmookler Reis, R.·Fedichev, P. O.
View original source ↗Export metadata ↓

Abstract

We collected 60 age-dependent transcriptomes for C. elegans strains including four exceptionally long-lived mutants (mean adult lifespan extended up to 9.4-fold) and three examples of RNAi treatments that increased lifespan by 19 - 35%. Principal Component Analysis (PCA) reveals aging as a transcriptomic drift along a single direction, consistent across the vastly diverse biological conditions and coinciding with the first principal component, a hallmark of the criticality of the underlying gene regulatory network. We, therefore, expected that the organisms aging state could be characterized by a single number closely related to vitality deficit or biological age. The \"aging trajectory\", i.e. the dependence of the biological age on chronological age, is then a universal stochastic function modulated by the network stiffness; a macroscopic parameter reflecting the network topology and associated with the rate of aging. To corroborate this view, we used publicly available datasets to define a transcriptomic biomarker of age and observed that the rescaling of age by lifespan simultaneously brings together aging trajectories of transcription and survival curves. In accordance with the theoretical prediction, the limiting mortality value at the plateau agrees closely with the mortality rate doubling exponent estimated at the cross-over age near the average lifespan. Finally, we used the transcriptomic signature of age to identify possible life-extending drug compounds and successfully tested a handful of the top ranking molecules in C. elegans survival assays and achieved up to a +30% extension of mean and median lifespan.

Source connections

Explore related subjects

genomicsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Tarkhov, A. E., Alla, R., Ayyadevara, S., Pyatnitskiy, M., Menshikov, L., Shmookler Reis, R., Fedichev, P. O.. 2017-10-23. Universal transcriptomic signature of age reveals temporal scaling of Caenorhabditis elegans aging trajectories. https://doi.org/10.1101/207647

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Gene Embedding Hub: a standardized resource for human gene representations

Gene embeddings are vector representations of gene identity that provide machine-learning models with information from diverse biological sources. However, their use is hindered by a lack of standardization: inconsistent identifiers, formats, and preprocessing conventions. In this work, we present a unified resource of 67 human gene-embedding sets derived from protein, DNA and RNA sequences, biomedical text, bulk expression data, single-cell expression models, functional data, biological networks, knowledge graphs, regulatory genomics and multimodal models, covering up to 20,097 GENCODE-annotated protein-coding genes. The collection includes both published precomputed embeddings and representations generated or extracted from publicly available models and biological data. Each embedding set is organized in a folder containing the embedding matrix, the Ensembl gene identifiers, machine-readable metadata, and processing documentation. We validate the resource by measuring global and local similarity, cross-embedding consensus, and cross-embedding predictability. The collection is designed to allow community-contributed embeddings that meet predefined technical and documentation requirements, enables comparison of gene representations across modalities and provides standardized embeddings for training and downstream applications.

genomics↗
bioRxiv2026

Twenty-five new microsporidian genomes: Insights into ploidy, reproduction, and the group's pangenome

Microsporidia are single-celled, obligately intracellular eukaryotic parasites of growing importance. Many aspects of their biology remain enigmatic, partly because of difficulties in sampling, culturing, and experimentally manipulating them. Here, we continue efforts to generate microsporidian genomes from serendipitously infected organisms sequenced for biodiversity genomics initiatives, such as the Darwin Tree of Life Project. We present 25 new microsporidian genomes: 14 biologically complete, including several at (near-)chromosome level, and 11 partial. Using RNA-seq data for three published genomes we identify Prokka as a suitable ab initio annotation approach for Microsporidia. Consistently annotating all available genomes, we investigate gene-content diversity across microsporidian clades. We find that the microsporidian pangenome exhibits extreme diversity, and that current genomic data substantially undersample the group's proteome space. Neither GC content nor genome span consistently explains orthogroup number across lineages, suggesting different evolutionary pressures. We find few one-to-one orthogroups in Microsporidia, as well as few orthogroups that are both lineage-specific and conserved across most species within a given lineage. Finally, Hi-C data confirm that tetraploid Amblyosporida microsporidia occur as two equivalent diploid units. In contrast, one Enterocytozoonida tetraploid genome suggests that all four genome copies occur within a single nucleus (a 'monokaryon'), confirming a previous proposal.

genomics↗
bioRxiv2026

The Braarudosphaera bigelowii genome reveals cellular remodeling around a nitrogen-fixing organelle

Braarudosphaera bigelowii hosts the nitrogen-fixing cyanobacterial organelle UCYN-A, or the nitroplast, but the absence of a reference genome has limited investigation of the genomic features accompanying this association. Here, we present nuclear and organellar genome resources for the cultured B. bigelowii strain FR-21. The assembly comprises a 472.1-Mb nuclear genome together with representative nitroplast, chloroplast, and mitochondrial genomes of 1.49 Mb, 107 kb, and 44 kb, respectively. The four genomic compartments have strongly differentiated GC compositions, consistent with their distinct evolutionary origins. The large nuclear genome does not appear to reflect a corresponding expansion of protein-coding capacity. Repeat annotation indicates that approximately 77% of the nuclear assembly is repetitive, leaving approximately 108 Mb of nonrepetitive sequence containing roughly 16,000 predicted protein-coding genes. Phylogenomic analysis places B. bigelowii within the expected diversity of haptophytes, indicating that its unusual diazotrophic lifestyle is not associated with an anomalous phylogenetic position. Comparative analysis of nitrogen metabolism genes reveals extensive remodeling of host nitrogen acquisition and assimilation. B. bigelowii lacks major components required for nitrate and nitrite assimilation and has reduced capacity to use urea, cyanate, and several internally recycled nitrogen sources. In contrast, ammonium transport and the glutamine synthetase-glutamate synthase pathway are retained. This combination suggests reduced flexibility in nitrogen use and a host metabolism increasingly centered on ammonium supplied by the nitroplast. B. bigelowii also encodes an expanded set of flavodoxin and cryptochrome genes. Eleven of 14 flavodoxin candidates and 21 of 39 cryptochrome candidates contained motifs linked to nitroplast targeting. Together with previous evidence that some of these proteins are abundantly imported into the nitroplast, these expansions point to host-encoded roles in nitroplast redox metabolism and diel regulation. These genome resources establish a foundation for investigating nitroplast protein import, host-organelle metabolic integration, and the genomic consequences of acquiring an intracellular nitrogen-fixing compartment. They further show that the evolution of the B. bigelowii-UCYN-A relationship involved substantial remodeling of genome architecture and nitrogen metabolism in both partners.

genomics↗