Biology subjects

Marques, P.

Publications and source records attributed to Marques, P..

4 recordsLinked to original sources

bioRxiv2026

SENOMORPHIC EFFECT OF GENETIC AND CHEMICAL PARTIAL REPROGRAMMING

Partial reprogramming has emerged as a promising strategy to ameliorate aging phenotypes, yet its cellular targets and mechanisms remain poorly defined. Cellular senescence is a central hallmark of aging and a plausible mediator of reprogramming-induced rejuvenation. Here we show that genetic and chemical partial reprogramming act directly on senescent cells without restoring proliferative capacity. OSKM expression or a reduced two-compound regimen, tranylcypromine and RepSox (2c), attenuates senescence-associated secretory activity, restores mitochondrial homeostasis and apoptotic priming, and improves functional and inflammatory parameters in aged mice, establishing senomorphic, identity-preserving reprogramming as a potentially safer aging intervention.

cell biology↗

bioRxiv2025

Pasta, an age-shift transcriptomic clock, maps the chemical and genetic determinants of aging and rejuvenation

With the growing burden of age-related diseases, understanding and modulating the aging process has become a priority. Transcriptomic aging clocks (TACs) can track biological age but remain limited by platform dependence, tissue specificity, or restricted accessibility. To address this, we developed Pasta, a robust and broadly applicable human TAC built using a novel age-shift learning framework. Pasta accurately predicted relative age across diverse tissues, data types, including bulk and single-cell RNA-Seq as well as microarray data, and species. Its predictions aligned with senescent and stem-like cellular states, with model coefficients enriched for p53 and DNA damage response pathways. Pastas age scores correlated with tumor grade and patient survival in several cancer types, indicating potential clinical relevance. Applied to the Connectivity Map L1000 dataset, Pasta identified both established and previously unrecognized age-modulatory compounds and genetic perturbations, highlighting mitochondrial translation and mRNA splicing as key determinants of cellular propensity for aging and rejuvenation, respectively. Experimental validation confirmed pralatrexate as a potent senescence inducer and piperlongumine as a rejuvenating agent. Together, these findings establish Pasta as a versatile and accessible tool for aging research and therapeutic discovery.

bioinformatics↗

bioRxiv2025

Larger fish in the headwaters: testing the drivers of longitudinal distribution in streams

Stream fishes often display distinct spatial patterns in size distribution, with one possible pattern being larger individuals dominating the headwaters. This "larger fish upstream pattern" (LFUP) has been widely documented, yet the ecological drivers remain unclear. We investigated factors contributing to LFUP in the fish community of a South American stream. Using historical data (1994-1998) from electrofishing surveys across six sites, we analyzed size distribution across eight species, with predictors including upstream distance, food availability, predation pressure, and intraspecific competition. Linear mixed models indicated that four species exhibit consistent LFUP, primarily driven by upstream distance or food availability. Species with pelagic or lithopelagic spawning displayed LFUP, supporting the hypothesis that LFUP is linked to reproductive strategies requiring upstream movement to maintain population stability. Our findings support that habitat connectivity and complexity are crucial for conserving small pelagic and lithopelagic fish species, as suggested in previous works. This study contributes to the field by highlighting mobile behavior in small tropical stream fishes and underscores the need for conservation strategies that account for movement patterns and habitat requirements in stream systems worldwide.

ecology↗

bioRxiv2023

Impact of prenatal synthetic glucocorticoid exposure on the adolescent brain

Synthetic Glucocorticoids (sGC) are commonly prescribed in preterm risk pregnancies in order to improve fetal organ maturation. This administration greatly reduces perinatal and neonatal mortality and respiratory distress syndrome associated with prematurity, but preclinical evidence warns for an adverse effect of sGC in the developing brain. In this work we evaluated the long-term effects of prenatal exposure to sGC in the brain of 17 years-old adolescents using multimodal MRI. From 4607 birth registrations from Hospital de Braga - Portugal, we selected participants that were born with similar gestational age, but that were either exposed during pregnancy to sGC (n=21) or non-exposed (n=24). After obtaining a detailed clinical history, participants were subjected to an extensive neuropsychological evaluation, followed by structural and functional MRI. No differences were found in the performance on neuropsychological tests between sGC-exposed and non-exposed participants. Moreover, no differences were found in regional brain volumes. However, the sGC-exposed group presented reduced functional connectivity at rest in a network involving primarily sub-cortical, cerebellar and frontal nodes in comparison to the non-exposed group, even after controlling for confounding factors such as gestational age at birth, birth weight, and sex. Our results suggest that prenatal sGC-exposed adolescents present no significant deviations in neuropsychological performance in the dimensions that we evaluated, although they presented altered functional connectivity, highlighting the need for additional studies to understand the impact of these changes in brain functioning and in behavior. HighlightsPrenatal synthetic glucocorticoid exposure does not lead to structural changes in the adolescent brain. Adolescents prenatally exposed to synthetic glucocorticoids present altered resting state network.

neuroscience↗