Biology subjects

Pabis, K.

Publications and source records attributed to Pabis, K..

4 recordsLinked to original sources

bioRxiv2026

Photographic age gap is associated with frailty and predicts survival in laboratory mice

Ageing studies in mice need biomarkers that are cheap, non-invasive and repeatable. We asked how much of a mouse's age can be read from an ordinary photograph, and whether the part that cannot be explained by age carries biological information. We assembled 2,846 photographs of 1,292 mice (four strains, 1 to 34 months old) from seven facilities and predicted age with a frozen self-supervised vision model (DINOv2) and a ridge regression, always tested on facilities the model had never seen. Absolute age transferred poorly between facilities (median absolute error 138 days), because each facility's photographs carried an offset. Relative age transferred well: among mice photographed in the same session, the older mouse was predicted older in 65% of pairs, rising above 95% for age differences over 500 days, and the later photograph of the same mouse was predicted older in 63% of repeat pairs. Sex, in comparison, was inferred more reliably (87%). Mice predicted older than their age were frailer (+0.12 SD per 100 days) and had shorter survival (hazard ratio 1.14 per 100 days), and fourth generation (G4) telomerase-deficient mice looked 151 days older than their wild-type controls. Routine photographs therefore carry a real biological age signal that can be read at no extra cost, best used to compare mice photographed together.

systems biology↗

bioRxiv2023

A stagewise response to mitochondrial dysfunction in mitochondrial DNA maintenance disorders

Mitochondrial DNA deletions clonally expand in skeletal muscle of patients with mtDNA maintenance disorders, impairing mitochondrial oxidative phosphorylation dysfunction. Previously we have shown that these mtDNA deletions originally arise and accumulate in the perinuclear mitochondria causing localised mitochondrial dysfunction before spreading through the muscle fibre. We believe that mito-nuclear signalling is a key contributor in this process. To further understand the role of mito-nuclear signalling, we use imaging mass cytometry to characterise the levels of mitochondrial respiratory complexes I-IV and ATP synthase alongside a mitochondrial mass marker, in a cohort of patients with mtDNA maintenance dosirders. We then expanded this panel to include protein markers of key signalling pathways to investigate the cellular response in fibres with different combinations of oxidative phosphorylation dysfunction and in ragged red fibres. We find CI and CIV deficiency to be most common, with a smaller proportion of cells that are also CIII and/or CV deficient. Interestingly, we also note that in cells deficient for one or more complexes, any complexes which are not deficient are commonly upregulated beyond the increase of mitochondrial mass typically observed in ragged red fibres. We further find that oxidative phosphorylation deficient fibres exhibit an increase in abundance of proteins involved in the proteostasis e.g. HSP60 and LONP1, and mitochondrial protein synthesis e.g. PHB1. Our analysis suggests that the cellular response to mitochondrial dysfunction changes depending on the combination of deficient oxidative phosphorylation complexes in each cell.

cell biology↗

bioRxiv2022

A concerted increase in readthrough and intron retention drives transposon expression during aging and senescence

Aging and senescence are characterized by pervasive transcriptional dysfunction, including increased expression of transposons and introns. Our aim was to elucidate mechanisms behind this increased expression. Most transposons are found within genes and introns, with a large minority being close to genes. This raises the possibility that transcriptional readthrough and intron retention are responsible for age-related changes in transposon expression rather than expression of autonomous transposons. To test this, we compiled public RNA-seq datasets from aged human fibroblasts, replicative and drug-induced senescence in human cells and RNA-seq from aging mice and senescent mouse cells. Indeed, our reanalysis revealed a correlation between transposons expression, intron retention and transcriptional readthrough across samples and within samples. Both intron retention and readthrough increased with aging or cellular senescence and these transcriptional defects were more pronounced in human samples as compared to those of mice. In support of a causal connection between readthrough and transposon expression, analysis of models showing induced transcriptional readthrough confirmed that they also show elevated transposon expression. Taken together, our data suggests that elevated transposon reads during aging seen in various RNA-seq dataset are concomitant with multiple transcriptional defects. Intron retention and transcriptional readthrough are the most likely explanation for the expression of transposable elements that lack a functional promoter.

bioinformatics↗

bioRxiv2020

Triplex and other DNA motifs show motif-specific associations with mitochondrial DNA deletions and species lifespan.

The "theory of resistant biomolecules" posits that long-lived species show resistance to molecular damage at the level of their biomolecules. Here, we test this hypothesis in the context of mitochondrial DNA (mtDNA) as it implies that predicted mutagenic DNA motifs should be inversely correlated with species maximum lifespan (MLS). First, we confirmed that guanine-quadruplex and direct repeat (DR) motifs are mutagenic, as they associate with mtDNA deletions in the human major arc of mtDNA, while also adding mirror repeat (MR) and intramolecular triplex motifs to a growing list of potentially mutagenic features. What is more, triplex motifs showed disease-specific associations with deletions and an apparent interaction with guanine-quadruplex motifs. Surprisingly, even though DR, MR and guanine-quadruplex motifs were associated with mtDNA deletions, their correlation with MLS was explained by the biased base composition of mtDNA. Only triplex motifs negatively correlated with MLS even after adjusting for body mass, phylogeny, mtDNA base composition and effective number of codons. Taken together, our work highlights the importance of base composition for the comparative biogerontology of mtDNA and suggests that future research on mitochondrial triplex motifs is warranted.

bioinformatics↗