Biology subjects

Aprahamian, F.

Publications and source records attributed to Aprahamian, F..

4 recordsLinked to original sources

bioRxiv2026

Glycometabolic, inflammatory and exocrine plasma proteins predict cancer in individuals with cardiovascular disease

Cancer development is preceded by systemic immune, metabolic and tissue perturbation. We asked whether a minimal circulating-protein signature anticipates incident cancer in patients with atheromatous cardiovascular disease (ACVD) exposed to tobacco. Discovery used a nested case-control set drawn from the longitudinal FLEMENGHO cohort (n=156; 38 incident lung cancers). Multi-omic profiling returned a two-step classifier: four proteins, smoking status, personal cancer history. Preprocessing constants, classifiers and both thresholds were fixed before transfer to PREVALUNG (n=397; 58 incident cancers, 26 of them lung). There, low O-GlcNAcase (OGA) with low interleukin-6 (IL-6) defined a very-low-risk stratum holding 1 of 58 cancers (sensitivity 98.3%, negative predictive value 98.8%); low chymotrypsin C (CTRC) with high beta microseminoprotein (MSMB) defined a high-risk stratum in which 15 of 28 participants developed cancer. No additional omic feature (metabolomic, immunophenotypic, clonal-haematopoietic or metagenomic) was retained as a reproducible improvement to the classifier under our selection framework. Discrimination was greater for cancers diagnosed more than 12 months after sampling than for near-term cancers (AUC 0.766, 95% CI 0.671-0.857, versus 0.589, 0.485-0.692), arguing against performance being driven principally by occult disease. These estimates are conditional on the cancer frequency of this population. They require prospective confirmation before any imaging schedule is changed.

cancer biology↗

bioRxiv2025

Taurine is a Natural Host Cytoadhesion Inhibitor in Asymptomatic Malaria Cases

The prolonged dry season in malaria-endemic regions of sub-Saharan Africa can be divided into periods of high and low transmission. The majority of symptomatic malaria cases are restricted to the short high transmission period that follows the rainy season. Shortly after, persistent asymptomatic malaria cases are more prevalent throughout the prolonged low transmission period. It is still unclear whether host metabolic alterations play a role in asymptomatic infections during seasonal malaria. In this study, we analyzed the blood plasma metabolome (n=199) of individuals in The Gambia, West Africa, capturing data from both high and low malaria transmission periods. Plasma samples from individuals (n=16) were collected monthly throughout the low transmission season, enabling a longitudinal analysis of metabolic alternations over six months. Our findings reveal that significant changes in host plasma metabolite composition are associated with seasonality and malaria pathogenicity. Notably, we observed elevated levels of taurine in asymptomatic malaria infections, especially during periods of low transmission. In vitro, this naturally occurring host molecule inhibits the cytoadhesion of malaria-infected red blood cells (iRBCs), which is key to malaria disease severity and mortality. Exogenous taurine can significantly reduce or reverse binding of iRBCs to the common adhesion receptor CD36 and the endothelial protein C receptor (EPCR), the later being associated with cerebral malaria. This study uncovers a mechanism by which elevated taurine plasma levels in asymptomatic infections could reduce cytoadhesion and lead to increased splenic clearance, thereby strengthening host resistance to symptomatic infections. In the absence of health strategies targeting dry season parasite reservoirs, our findings highlight taurine as a potential prophylactic or therapeutic agent to reduce symptomatic malaria in sub-Saharan Africa. One Sentence SummaryMetabolomics uncovers taurine as a natural host inhibitor of Plasmodium falciparum cytoadhesion in asymptomatic malaria carriers, offering new insights for disease control.

microbiology↗

bioRxiv2022

Smurfness-based two-phase model of ageing helps deconvolve the ageing transcriptional signature

Ageing is characterised at the molecular level by six transcriptional hallmarks of ageing, that are commonly described as progressively affected as time passes. By contrast, the Smurf assay separates high-and-constant-mortality risk individuals from healthy, zero-mortality risk individuals, based on increased intestinal permeability. Performing whole body total RNA sequencing, we found that Smurfness distinguishes transcriptional changes associated with chronological age from those associated with biological age. We show that transcriptional heterogeneity increases with chronological age in non-Smurf individuals preceding the other five hallmarks of ageing, that are specifically associated with the Smurf state. Using this approach, we also devise targeted pro-longevity genetic interventions delaying entry in the Smurf state. We anticipate that increased attention to the evolutionary conserved Smurf phenotype will bring about significant advances in our understanding of the mechanisms of ageing. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=150 HEIGHT=200 SRC="FIGDIR/small/517330v5_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@37b39org.highwire.dtl.DTLVardef@8ef8f0org.highwire.dtl.DTLVardef@797299org.highwire.dtl.DTLVardef@1529b0d_HPS_FORMAT_FIGEXP M_FIG The two-phase model of ageing allows to study separately the effect of chronological and physiological age. (A) Classic approaches for studying ageing tend to consider it as a black box affecting all individuals progressively from birth to death. Instead, the Smurf phenotype shows that life can be divided into two consecutive phases separated by an abrupt transition. (B) All individuals undergo this transition at a different moment in their life, prior to death. This allows us to switch from population based approaches, comparing bulks of age-matched individuals through time, to individuals-centred approaches relying on direct access to their transition status. (C) Such paradigm shift shows that hallmarks of ageing long thought to progressively change with age are actually mostly affected in a growing proportion of Smurfs, allowing for the identification of the chain of events accompanying ageing and death from natural causes. (D) By studying the behaviour of the ageing transcriptome as a function of chronological age and Smurfness separately, we demonstrate that the progressively changing transcriptional ageing signature, as described in Frenk & Houseley (2018), is in fact the convolution changes accompanying chronological age signature (increased transcriptional noise) and changes associated with Smurfness (or biological age) signature (increased stress response and inflammation, decreased expression of ribosomal and mitochondrial genes). We also identified a hallmark partially associated with only old Smurfs (ATH5), suggesting that chronological age can affect, late in life, the Smurf response. C_FIG

systems biology↗

bioRxiv2022

Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming

The expression of the pluripotency factors OCT4, SOX2, KLF4 and MYC (OSKM) can convert somatic differentiated cells into pluripotent stem cells in a process known as reprogramming. Notably, cycles of brief OSKM expression do not change cell identity but can reverse markers of aging in cells and extend longevity in progeroid mice. However, little is known about the mechanisms involved. Here, we have studied changes in the DNA methylome, transcriptome and metabolome in naturally aged mice subject to a single period of transient OSKM expression. We found that this is sufficient to reverse DNA methylation changes that occur upon aging in the pancreas, liver, spleen and blood. Similarly, we observed reversion of transcriptional changes, especially regarding biological processes known to change during aging. Finally, some serum metabolites altered with aging were also restored to young levels upon transient reprogramming. These observations indicate that a single period of OSKM expression can drive epigenetic, transcriptomic and metabolomic changes towards a younger configuration in multiple tissues and in the serum.

cell biology↗