Biology subjects

Caravia, X. M.

Publications and source records attributed to Caravia, X. M..

3 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↗

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↗

bioRxiv2022

miR-29 is an important driver of aging-related phenotypes

Aging is a consequence of complex molecular changes, but the roles of individual microRNAs (miRNAs) in aging remain unclear. One of the few miRNAs that are upregulated during both normal and premature aging is miR-29. We confirmed this finding in our study in both mouse and monkey models. Follow-up analysis of the transcriptomic changes during normal aging revealed that miR-29 is among the top miRNAs predicted to drive the aging-related gene expression changes. We also showed that partial loss of miR-29 extends the lifespan of Zmpste24-/- mice, an established model of progeria, which indicates that miR-29 is functionally important in this accelerated aging model. To examine whether miR-29 upregulation alone is sufficient to promote aging-related phenotypes in vivo, we generated mice in which miR-29 can be conditionally overexpressed (miR-29TG). We found that miR-29 overexpression in mice is sufficient to drive aging-related phenotypes including alopecia, kyphosis, osteoporosis, senescence, and leads to early lethality. Transcriptomic analysis of both young miR-29TG and old WT mice revealed shared downregulation of genes enriched in extracellular matrix and fatty acid metabolism, and shared upregulation of genes in pathways linked to inflammation. Together, these results highlight the functional importance of miR-29 in controlling a gene expression program that drives agingrelated phenotypes.

physiology↗