Mariona Jové

Universitat de Lleida | UDL · Biomedical Research Institute

Aging biology entails a cell/tissue deregulated metabolism that affects all levels of biological organization. Therefore, the application of "omic" techniques that are closer to phenotype, such as metabolomics, to the study of the aging process should be a turning point in the definition of cellular processes involved. The main objective of the pre...

The strong interest shown in the study of the causes of aging in recent decades has uncovered many mechanisms that could contribute to the rate of aging. These include mitochondrial ROS production, DNA modification and repair, lipid peroxidation-induced membrane fatty acid unsaturation, autophagy, telomere shortening rate, apoptosis, proteostasis,...

Mitochondria play a wide diversity of roles in cell physiology and have a key functional implication in cell bioenergetics and biology of free radicals. As the main cellular source of oxygen radicals, mitochondria have been postulated as the mediators of the cellular decline associated with the biological aging. Recent evidences have shown that mit...

One of the richest tissues in lipid content and diversity of the human body is the brain. The human brain is constitutively highly vulnerable to oxidative stress. This oxidative stress is a determinant in brain aging, as well as in the onset and progression of sporadic (late-onset) Alzheimer’s disease (sAD). Glycerophospholipids are the main lipid...

It is assumed that the human brain is especially susceptible to oxidative stress, based on specific traits such as a higher rate of mitochondrial free radical production, a high content in peroxidizable fatty acids, and a low antioxidant defense. However, it is also evident that human neurons, although they are post-mitotic cells, survive throughou...

Background: Obstructive sleep apnoea (OSA) has a high prevalence in patients with Alzheimer's disease (AD). Both conditions have been shown to be associated with lipid dysregulation. However, the relationship between OSA severity and alterations in lipid metabolism in the brains of patients with AD has yet to be fully elucidated. In this context, w...

Methionine constitutes a central hub of intracellular metabolic adaptations leading to an extended longevity (maximum lifespan). The present study follows a comparative approach analyzing methionine and related metabolite and amino acid profiles using an LC-MS/MS platform in the hearts of seven mammalian species with a longevity ranging from 3.8 to...

Background Delaying the transition from minimal cognitive impairment to Alzheimer’s dementia is a major concern in Alzheimer’s disease (AD) therapeutics. Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet effective substances are recommended. The...

Aims: Non-targeted lipidomics analysis was conducted in post-mortem human frontal cortex area 8 (GM) and white matter of the frontal lobe centrum semi-ovale (WM) to identify lipidomes in middle-aged individuals with no neurofibrillary tangles and senile plaques, and cases at progressive stages of sporadic Alzheimer's disease (sAD). Methods: Lipidom...

Background Obstructive sleep apnoea (OSA) is the most frequent form of sleep-disordered breathing in patients with Alzheimer’s disease (AD). Available evidence demonstrates that both conditions are independently associated with alterations in lipid metabolism. However, it is unknown whether the expression of lipids is different between AD patients...

Dipeptidyl peptidase 9 (DPP9) is a member of the dipeptidyl peptidase IV family. Inhibition of DPP9 has recently been shown to activate the nucleotide-binding domain leucine-rich repeat 1 (NLRP1) inflammasome. NLRP1 is known to bind nucleic acids with high affinity and directly interact with double stranded RNA, which plays a key role in viral repl...

Decreased content and activity of the mechanistic target of rapamycin (mTOR) signalling pathway, as well as the mTOR complex 1 (mTORC1) itself, are key traits for animal species and human longevity. Since mTORC1 acts as a master regulator of intracellular metabolism, it is responsible, at least in part, for the longevous phenotype. Conversely, incr...

Transient ischemic attacks (TIAs) before an acute ischemic stroke (AIS) could induce ischemic tolerance (IT) phenomena. with an endogenous neuroprotective role (Ischemic preconditioning. IPC). A consecutive prospective cohort of patients with AIS were recruited from 8 different hospitals. Participants were classified by those with non-previous rece...

Extracellular vesicles (EVs) constitute an intricate system of molecular exchange that has recently gained tremendous interest. However, sustainable sources of safe biological EVs remain scarce and elusive. This study explores and defines the use of food industry by‐products (BP) as a circular source of safe biocompatible EVs. Averaged diameter and...

Methionine constitutes a central hub of intracellular metabolic adaptations leading to an extended longevity (maximum lifespan). The present study follows a comparative approach analyzing methionine and related metabolites and amino acids profiles using a LC-MS/MS platform in heart from seven mammalian species with a longevity ranging from 3.8 to 5...

Metabolomic profiling analysis has the potential to highlight new molecules and cellular pathways that may serve as potential therapeutic targets for disease treatment. In this study, we used an LC-MS/MS platform to define, for the first time, the specific metabolomic signature of uterine serous carcinoma (SC), a relatively rare and aggressive vari...

To the Editor We thank Dr. Buschard et al. for their interest in our study (1) and for sharing their results. In our study, we defined three groups of the healthy populations (adults, old, and centenarians) to characterize changes in centenarians versus mature and old people focusing on sphingolipidome. Sphingolipids are a relatively little-studied...

Growing evidence implicates the gut microbiome in cognition. Blastocystis is a common gut single-cell eukaryote parasite frequently detected in humans but its potential involvement in human pathophysiology has been poorly characterized. Here we describe how the presence of Blastocystis in the gut microbiome was associated with deficits in executive...

Fatty acids are key components in the structural diversity of lipids and play a strategic role in the functional properties of lipids which determine the integrity of neuronal and glial cell membranes, the generation of lipid signaling mediators, and the chemical reactivity of acyl chains. The present study analyzes using gas chromatography the fat...

Introduction Obstructive sleep apnea (OSA) is a chronic, heterogeneous and multicomponent disorder with associated cardiovascular and metabolic alterations. Despite being the most common sleep-disordered breathing, it remains a significantly undiagnosed condition. Objective We examined the plasma metabolome and lipidome of patients with suspected...

A species-specific lipidome profile is an inherent feature linked to longevity in the animal kingdom. However, there is a lack of lipidomic studies on human longevity. Here we use mass spectrometry based lipidomics to detect and quantify 151 sphingolipid molecular species and use these to define a phenotype of healthy humans with exceptional lifesp...

Lipids are closely associated with brain structure and function. However, the potential changes in the lipidome induced by aging remain to be elucidated. In this study, we used chromatographic techniques and a mass spectrometry-based approach to evaluate age-associated changes in the lipidome of the frontal cortex and cerebellum obtained from adult...

Soya consumption can decrease oxidative stress in animal models. Moreover, phytoestrogens such as genistein, present in soya, can mimic some of the beneficial effects of estrogens and are devoid of significant side effects, such as cancer. In this study, we have performed a controlled lifelong study with male OF1 mice that consumed either a soya-fr...

Scope Diets with low content in advanced glycation endproducts (AGEs) lead to beneficial properties in highly prevalent age-related diseases. To shed light on the mechanisms behind, we analyzed the changes induced by a low AGE dietary intervention in the circulating metabolome. Methods and results To this end, 20 non-diabetic patients undergoing p...

Celiac disease (CD) is an autoimmune enteropathy linked to alterations of metabolism. Currently, limited untargeted metabolomic studies evaluating differences in the plasma metabolome of CD subjects have been documented. We engage in a metabolomic study that analyzes plasma metabolome in 17 children with CD treated with a gluten-free diet and 17 he...

Since amyotrophic lateral sclerosis cases exhibit significant heterogeneity, we aim to investigate the association of lipid composition of plasma and cerebrospinal fluid with amyotrophic lateral sclerosis diagnosis, its progression, and clinical characteristics. Lipidome analyses would help to stratify patients on a molecular basis. For this reason...

Introduction Human prefrontal cortex (hPFC) is a recent evolutionarily developed brain region involved in cognitive functions. Human cognitive functions decline during aging. Yet the molecular mechanisms underlying the functional deterioration of the neural cells of this brain region still remain to be fully described. Areas covered In this review...

Current shreds of evidence point to the entorhinal cortex (EC) as the origin of the Alzheimer’s disease (AD) pathology in the cerebrum. Compared with other cortical areas, the neurons from this brain region possess an inherent selective vulnerability derived from particular oxidative stress conditions that favor increased mitochondrial molecular da...

Introduction Fatty acids are essential nutrients for the fetus and are supplied by the mother through the placenta. Desaturase and elongase enzymes play an important role in modulating the fatty acid composition of body tissues. We aimed to compare the fatty acid profile and the estimated desaturase and elongase activities in the placenta of approp...

Nucleocytosolic transport, a membrane process, is impaired in motor neurons in amyotrophic lateral sclerosis (ALS). This study analyzes the nuclear lipidome in motor neurons in ALS, and examines molecular pathways linked to the major lipid alterations. Nuclei were obtained from the frozen anterior horn of the lumbar spinal cord of ALS patients and...

The microbiota-gut-brain axis has emerged as a novel target in depression, a disorder with low treatment efficacy. However, the field is dominated by underpowered studies focusing on major depression not addressing microbiome functionality, compositional nature, or confounding factors. We applied a multi-omics approach combining pre-clinical models...

Species longevity varies significantly across animal species, but the underlying molecular mechanisms remain poorly understood. Recent studies and omics approaches suggest that phenotypic traits of lon-gevity could converge in the mammalian target of rapamycin (mTOR) signalling pathway. The present study focuses on the comparative approach in heart...

Background Inhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits. Methods We studied gut microbiome composition and functionality, and plasma and faecal metabolomics in association with cognitive tests evalua...

Complex I, a component of the electron transport chain, plays a central functional role in cell bioenergetics and the biology of free radicals. The structural and functional N‐module of complex I is one of the main sites of the generation of free radicals. The NDUFV2 subunit/N1a cluster is a component of this module. Furthermore, the rate of free r...

Like other human body cell systems the human brain is a target of the physiological aging process. Specific regions of the human brain exhibit differential vulnerabilities to aging. Yet the basic molecular mechanisms that underlie the preservation or deterioration of neurons and cerebral functions are little known. In this chapter, we focus attenti...

Aim: Peroxisomes play a key role in lipid metabolism, and peroxisome defects have been associated with neurodegenerative diseases such as X-adrenoleukodystrophy and Alzheimer's disease. The present study aims to elucidate the contribution of peroxisomes in lipid alterations of area 8 of the frontal cortex in the spectrum of TDP43-proteinopathies. C...

Celiac disease (CD) is an autoimmune enteropathy associated with alterations of metabolism. Metabolomics studies, although limited, showed changes in choline, choline-derived lipids, and methionine concentrations, which could be ascribed to alterations in one-carbon metabolism. To date, no targeted metabolomics analysis investigating differences in...

The nonenzymatic adduction of malondialdehyde (MDA) to the protein amino groups leads to the formation of malondialdehyde-lysine (MDALys). The degree of unsaturation of biological membranes and the intracellular oxidative conditions are the main factors that modulate MDALys formation. The low concentration of this modification in the different cell...

The gut microbiome has been linked to fear extinction learning in animal models. Here, we aimed to explore the gut microbiome and memory domains according to obesity status. A specific microbiome profile associated with short-term memory, working memory, and the volume of the hippocampus and frontal regions of the brain differentially in human subj...

Lipids were determinants in the appearance and evolution of life. Recent studies disclose the existence of a link between lipids and animal longevity. Findings from both comparative studies and genetics and nutritional interventions in invertebrates, vertebrates, and exceptionally long-lived animal species-humans included-demonstrate that both the...

Egg-yolk based supplements have demonstrated biological effects. We have developed a novel processed egg-yolk (PEY) complement, and we have tested whether it has inflammation modulatory properties. These were evaluated in a lipopolysaccharide (LPS)-challenge in 1-month male rats by in vivo circulating cytokine profiles measured by multiplexing tech...

Species longevity varies significantly across animal species, but the underlying molecular mechanisms remain poorly understood. Recent studies and omics approaches suggest that phenotypic traits of longevity could converge in the mammalian target of rapamycin (mTOR) signalling pathway. The present study focuses on the comparative approach in heart...

Mitochondrial reactive oxygen species (ROS) production, specifically at complex I (Cx I), has been widely suggested to be one of the determinants of species longevity. The present study follows a comparative approach to analyse complex I in heart tissue from 8 mammalian species with a longevity ranging from 3.5 to 46 years. Gene expression and prot...

As obesity incidence is alarmingly rising among young individuals, we aimed to characterize an experimental model of this situation, considering the similarity between human and porcine physiology. For this reason, we fed prepubertal (63 days-old) Duroc breed females (n=20) either with a standard growth diet (3800 KCal/day) or one with a high-calor...

Human brain evolution toward complexity has been achieved with increasing energy supply as the main adaptation in brain metabolism. Energy metabolism, like other biochemical reactions in aerobic cells, is under enzymatic control and strictly regulated. Nevertheless, physiologically uncontrolled and deleterious reactions take place. It has been prop...

Background: Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors. Methods: We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liqui...

Background We wanted to define metabolomic patterns in plasma to predict a negative outcome in severe trauma patients. Methods A prospective pilot study was designed to evaluate plasma metabolomic patterns, established by liquid chromatography coupled to mass spectrometry, in patients allocated to an intensive care unit (in the University Hospital...

PGC-1α controls, to a large extent, the capacity of cells to respond to changing nutritional requirements and energetic demands. The key role of metabolic reprogramming in tumor development has highlighted the potential role of PGC-1α in cancer. To investigate how loss of PGC-1α activity in primary cells impacts the oncogenic characteristics of spo...

Methionine restriction (MetR) in animal models extends maximum longevity and seems to promote renoprotection by attenuating kidney injury. MetR has also been proven to affect several metabolic pathways including lipid metabolism. However, there is a lack of studies about the effect of MetR at old age on the kidney metabolome. In view of this, a mas...

Metformin is one of the treatments used for PCOS pathology decreasing body weight, plasma androgen, FSH and glucose levels. Unfortunately, there is little known about metformin’s effects on lipid metabolism, a crucial process in PCOS pathology. We have employed a lipidomic approach to explore alterations in the plasma lipid profile of patients with...

Multiple sclerosis (MS) is a complex multifactorial neuropathology. Although its etiology remains unclear, it has been demonstrated that the immune system attacks myelin, leading to demyelination and axonal damage. The involvement of lipids as one of the main components of myelin sheaths in MS and other demyelinating diseases has been postulated. H...

In this pilot study, we show that nuclei in spinal cord from ALS patients exhibit a differential lipidomic signature. Among the differential lipid species we could annotate 41 potential identities. These comprise membrane-bound lipids such as phosphatidylethanolamines -including plasmalogens- and phosphatidylcholines but also other lipid classes su...

Aim: Advanced glycation end-products (AGEs) have been involved in the atherogenic process in the high-risk population. The goal of this study was to demonstrate that AGEs are related to subclinical atheromatous disease in subjects with low to moderate vascular risk. Methods: A cross-sectional study in which 2,568 non-diabetic subjects of both sexes...

Human prefrontal cortex (PFC) is a recently evolutionary emerged brain region involved in cognitive functions. Human cognitive abilities decline during aging. Yet the molecular mechanisms that sustain the preservation or deterioration of neurons and PFC functions are unknown. In this review, we focus on the role of lipids in human PFC aging. As the...

A lipid profile resistant to oxidative damage is an inherent trait associated with animal lifespan. However, there is a lack of lipidomic studies on human longevity. Here we use mass spectrometry based technologies to detect and quantify 137 ether lipids to define a phenotype of healthy humans with exceptional lifespan. Ether lipids were chosen bec...

The human brain is a target of the aging process like other cell systems of the human body. Specific regions of the human brain exhibit differential vulnerabilities to the aging process. Yet the underlying mechanisms that sustain the preservation or deterioration of neurons and cerebral functions are unknown. In this review, we focus attention on t...

Background/Aims: Thyroid hormones have been recently linked to senescence and longevity. Given the recent description of TSHB mRNA in human adipose tissue (AT), we aimed to investigate the relationship between local AT TSH and adipose tissue senescence. Methods: TSHB mRNA (measured by real-time PCR) and markers of adipose tissue senescence [BAX, DB...

In biological systems lipids generate membranes and have a key role in cell signaling and energy storage. Therefore, there is a wide diversity of molecular lipid expressed at the compositional level in cell membranes and organelles, as well as in tissues, whose lipid distribution remains unclear. Here, we report a mass spectrometry study of lipid a...