Biology subjects

Roiz-Valle, D.

Publications and source records attributed to Roiz-Valle, D..

4 recordsLinked to original sources

bioRxiv2026

The aging modulator miR-29 is essential for adult cardiomyocyte function

Aging is the main risk factor for cardiovascular diseases, underscoring the need to identify the molecular regulators that sustain cardiac function during aging. The microRNA miR-29 is a well-established aging-associated regulator as its expression increases with age, and its overexpression promotes premature aging. Here, we define the cardiomyocyte-autonomous role of miR-29 in the adult heart by generating an inducible, cardiomyocyte-specific miR-29-deficient mouse model (Heart-iKO). We show that Heart-iKO mice develop dilated cardiomyopathy (DCM) with reduced ejection fraction that ultimately leads to premature death. Mechanistically, Heart-iKO cardiomyocytes exhibit alterations in mitochondrial structure and function. Transcriptomic profiling of bulk heart tissue and isolated cardiomyocytes revealed a consistent downregulation of genes involved in oxidative phosphorylation and the electron transport chain. We further observed a similar pattern of mitochondrial impairment in miR-29-deficient human cardiomyocytes derived from induced pluripotent stem cells (CM-iPSCs). Together, these findings highlight the context-dependent role of miR-29 in cardiac physiology and aging: although its upregulation promotes premature aging, its basal expression is required to maintain mitochondrial homeostasis and prevent heart failure in the adult myocardium.

physiology↗

bioRxiv2026

FAβ-gal: an automated fluorescence-based quantification of the senescence-associated beta-galactosidase X-gal assay

Cellular senescence plays a pivotal role in aging and cancer, two major biomedical and socioeconomic challenges of our time. Therefore, its study has become crucial for the design of interventions based on its manipulation. In this sense, researchers have developed a wide variety of techniques to detect and quantify cellular senescence. Among them, the most popular is the original Senescence-Associated {beta}-galactosidase (SA-{beta}-gal) colorimetric assay, based on the use of the chromogenic substrate X-gal. This compound is cleaved by {beta}-galactosidase, producing an insoluble, blue precipitate of 5,5-dibromo-4,4-dichloro-indigo (commonly referred to as indigo). While this method remains the gold standard senescence assay, its quantification remains challenging due to the color-based readout. In this work, we describe a method, which we have named FA{beta}-gal (Fluorescence Analysis of {beta}-galactosidase), that exploits the far-red fluorescence of the {beta}-gal product indigo and allows the quantification of SA-{beta}-gal activity under any conventional wide-field fluorescence microscopy using the original X-gal assay. In addition, we developed workflows and software applications that standardize SA-{beta}-gal quantification in a semiautomatic and unbiased manner. We demonstrate that FA{beta}-gal measurements present a strong linear correlation with the percentage of senescent cells and show high sensitivity. Moreover, we show that this method is also applicable to tissue sections, underscoring the versatility of our approach. Therefore, FA{beta}-gal could be easily introduced into the routine of laboratories already using the original colorimetric assay, enhancing the accuracy, sensitivity and reproducibility of senescence detection.

cell biology↗

bioRxiv2025

Reduced systemic autophagy by simultaneous loss of ATG4B, ATG4C and ATG4D leads to accelerated aging in mice

Autophagy is an essential catabolic pathway that safeguards cellular and tissue homeostasis, yet the systemic consequences of its impairment in mammals remain poorly defined because complete autophagy ablation is embryonic or perinatal lethal. Here, we generate ATG4A-only mice, a model in which ATG4A is the sole remaining ATG4 protease due to combined ATG4B/C/D deletion. Through comprehensive biochemical and cellular analyses, we delineate the in vivo substrate specificity of ATG4A and demonstrate that it sustains only minimal ATG8 priming, uncovering a previously unrecognized functional asymmetry within the mammalian ATG4-ATG8 system. ATG4A-only mice exhibit a profound but incomplete whole-body autophagy deficiency that disrupts multiple organ systems and triggers a premature aging syndrome marked by increased DNA damage, systemic senescence, metabolic dysfunction, and dramatically shortened lifespan. Integrating these findings with comparisons to additional ATG4-deficient models, we show that organismal longevity scales with residual autophagic competence. Together, our work reveals how graded reductions in autophagy integrity influence tissue fitness and aging, establishing autophagic capacity as a key determinant of mammalian lifespan.

cell biology↗

bioRxiv2024

miR-29a-3p, a new myokine orchestrating resistance exercise via coordinated metabolic responses

It remains unclear whether the adaptive response to different exercise models is mediated by EV miRNAs released from skeletal muscle and their functional metabolic role. We sequenced miRNA-loaded plasma EVs obtained from resting mice after 4-weeks endurance or resistance training. Resistance exercise increased the expression of a 11-miRNA profile grouped into two functional clusters. Using both genetically modified animal models and in vitro approaches, we have identified miR-29a-3p as a novel myokine secreted into the bloodstream as EV cargo by contracting skeletal muscle. It is a cornerstone in the adaptation to resistance training by mediating the coordinated expression and secretion of other miRNAs and affecting muscle mass development and energy metabolism in muscle and liver. Taken together, our study suggests a coordinating and determinant role of miR-29a-3p in the response and adaptation to resistance training, possibly due to its role as a myokine through its regulatory role in energy metabolism.

molecular biology↗