Tamas Fulop

• Université de Sherbrooke

Background Alzheimer's disease (AD) is a chronic brain degenerative disease that leads to dementia. Objective The aim of the present study is to investigate the neuroprotective impact of sodium-glucose cotransporter-2 inhibitors (SGLT2i) (empagliflozin and dapagliflozin) on tau phosphorylation, oxidative stress, and neuroinflammation. Methods We...

Background Parkinson’s Disease (PD) is associated with dysregulated/chronic inflammation. The immune system has multiple roles including beneficial effects such as clearing alpha synuclein aggregates. However, peripheral immune cells entering the brain may also contribute to inflammation and neurodegeneration. To identify which cells might have a n...

Background The perplex interrelation between circulating extracellular vesicles (cEVs) and amyloid-β (Aβ) deposits in the context of Alzheimer’s disease (AD) is poorly understood. Objective This study aims to 1) analyze the possible cross-linkage of the neurotoxic amyloid-β oligomers (oAβ) to the human cEVs, 2) identify cEVs corona proteins associ...

Alzheimer's disease (AD) is an age‐related neurodegenerative pathology. Brain‐derived extracellular vesicles (EVs) have been demonstrated to be implicated in AD pathogenesis by facilitating the propagation of Tau, amyloid‐β and inflammatory cytokines. However, the impact of peripheral EVs (pEVs) in AD pathogenesis remains poorly investigated. The o...

Introduction: Ageism, defined as stereotype, prejudice, and discrimination against people based on their age, has been shown to have unfavorable impacts on health. While discrimination has often been shown to negatively impact health, whether ageism might accelerate biological aging itself is unclear. Methods: We conducted secondary analyses of the...

Oxidative stress is characterized by the diminished capacity of a biological system to overcome the overproduction of reactive species (RS) and free radicals (FR). This process has been related to the pathogenesis of virtually every disease. Since this process is a leading cause of many diseases (e.g., ischemic stroke, heart failure, hypertension,...

Neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), represent a growing social, economic, and health burden worldwide. Several molecular alterations and pathogenic factors including oxidative stress have been proposed to explain their etiology. In fact, previously published human studies reported an elevated...

Background: Oxidative stress and chronic inflammation, at both the systemic and the central level, are critical early events in atherosclerosis and Alzheimer’s disease (AD). Purpose: To investigate the oxidative stress-, inflammation-, and Tau-phosphorylation-lowering effects of pomegranate polyphenols (PPs) (punicalagin, ellagic acid, peel, and ar...

Senile amyloid plaques are one of the main hallmarks of Alzheimer’s disease (AD). They correspond to insoluble deposits of amyloid-β peptides (Aβ) and are responsible for the inflammatory response and neurodegeneration that lead to loss of memory. Recent data suggest that Aβ possess antimicrobial and anti-viral activity in vitro. Here, we have used...

The brain was once considered as an immunoprivileged organ, mainly due to a tight blood-brain barrier. However, recent research shows that immune cells are participating in the surveillance, homeostasis and functioning of the brain. These typically also include brain-resident immune cells such as microglia, astrocytes and specialised T cells. This...

Sensory functions of organs of the head and neck allow humans to interact with the environment and establish social bonds. With aging, smell, taste, vision, and hearing decline. Evidence suggests that accelerated impairment in sensory abilities can reflect a shift from healthy to pathological aging, including the development of Alzheimer's disease...

Background It has been suggested that the acute natural killer (NK) cell response to aerobic exercise might contribute to the tumor suppressor effect of regular exercise observed in preclinical studies. Moreover, because this response is modulated by exercise intensity, high-intensity intervals exercise (HIIE) might represent an interesting therape...

Aging remains a mysterious process, but age-associated changes in the different organ systems constituting the whole organism are well known. One of the best studied both integrative and integrated system of the organism is the immune system, widely studied in relation to aging. These changes are considered as mostly detrimental as the name of immu...

The geroscience hypothesis – that by intervening on the basic biological mechanisms of aging we could simultaneously reduce the risks of many chronic diseases and dramatically improve healthspan – has garnered substantial traction and enthusiasm in the past decade. And indeed, if successful, there is enormous potential to reduce the burden of disea...

Cellular senescence was first defined as replicative senescence after the works of Hayflick. Later this concept was extended to many other pathways by which senescence is induced, mostly related to stresses inducing some type of DNA damage. Currently, cellular senescence is studied particularly in relation to aging and cancer. Data from animal expe...

During each cell’s life, myriads of different, necessary proteins are manufactured and serve as interacting structural and/or functional elements without which the cell could not function properly. Organismal and cellular aging imposes stresses, constrains and dysfunctions on each and every stage of protein manufacturing, maturation and maintenance...

Simple Summary Cancer-related fatigue is a prevalent symptom, with a significant impact on the daily lives of those affected. While physical exercise has demonstrated effectiveness in reducing the intensity and duration of fatigue, the literature still lacks sufficient evidence on the physiological mechanisms explaining this impact. This conceptual...

Aging is an important risk factor for cardiovascular diseases and convincing data have shown that chronic low-grade inflammation, which develops with advanced age, contributes significantly to cardiovascular risk. The present study aimed to use 18F-FDG/18F-NaF-PET/CT imaging to, respectively, gauge arterial inflammation and microcalcification in a...

Background: Aging is an important risk factor for cardiovascular diseases and con-vincing data has shown that chronic low-grade inflammation, which develops with advanced age, contributes significantly to cardiovascular risk. Objectives: The present study aimed to use ¹⁸F-FDG/¹⁸F-NaF-PET/CT imaging to respectively gauge arterial inflammation and mi...

Alzheimer disease (AD) is a disastrous neurodegenerative disease for which presently no consensus exists neither for the etiology nor for the efficacity of treatments. The amyloid hypothesis of the disease pathogenesis predominated during decades stating that amyloid beta (Aβ) formation and oligomerization is the major cause for AD. Recently, besid...

Background Over the past five years, the hypothesis linking periodontitis to Alzheimer’s disease (AD) has gained significant traction even though little is known about the underlying mechanisms driving this association. Periodontitis is caused by the dysbiosis of the dental biofilm, an extra‐cellular matrix produced by bacteria, which is mostly cau...

Protein structure analysis and classification, which is fundamental for predicting protein function, still poses formidable challenges in the fields of molecular biology, mathematics, physics and computer science. In the present work we exploit recent advances in computational topology to define a new intrinsic unsupervised topological fingerprint...

Citation: Alami, M.; Boumezough, K.; Khalil, A.; Ramchoun, M.; Boulbaroud, S.; Fulop, T.; Morvaridzadeh, M.; Berrougui, H. The Modulatory Bioeffects of Pomegranate (Punica granatum L.) Polyphenols on Metabolic Disorders: Understanding Their Preventive Role against Metabolic Syndrome. Nutrients 2023, 15, 4879. https:// Abstract: Modern research achi...

Modern research achievements support health-promoting effects of natural products and diets rich in polyphenols. Pomegranate (PG) (Punica granatum L.) contain a considerable number of bioactive compounds that exert a broad spectrum of beneficial biological activities, including antimicrobial, antidiabetic, antiobesity, and atheroprotective properti...

Background: Tumor-bearing animal studies have suggested that each aerobic exercise bout may acutely promote the infiltration of effector CD8+ cytotoxic T-cells (CTLs) in tumoral tissue and enhance the anti-tumor immune response. Exercise intensity being the main driver of this acute immune response, high-intensity interval exercise (HIIE) might be...

Background: It has been suggested that the acute natural killer (NK) cell response to aerobic exercise might contribute to the tumor suppressor effect of regular exercise observed in preclinical studies. Moreover, because this response is modulated by exercise intensity, high-intensity intervals exercise (HIIE) might represent an interesting therap...

Unlabelled: Atherosclerosis is an immuno-inflammatory process underlying cardiovascular diseases. One of the main actors of this inflammation is monocytes, with the switch in their phenotypes and irregularities in their cytokine production. Objective: This study was aimed to investigate the nutraceutical potential of extra virgin olive oil (EVOO...

Introduction: Clinically, Alzheimer's disease (AD) is a syndrome with a spectrum of various cognitive disorders. There is a complete dissociation between the pathology and the clinical presentation. Therefore, we need a disruptive new approach to be able to prevent and treat AD. Areas covered: In this review, the authors extensively discuss the...

This paper reports the proceedings of a virtual meeting convened by the European Interdisciplinary Council on Ageing (EICA), to discuss the involvement of infectious disorders in the pathogenesis of dementia and neurological disorders leading to dementia. We recap how our view of the infectious etiology of dementia has changed over the last 30 year...

Unlabelled: This study aimed to determine the size and distribution of LDL and HDL particles in North African acute coronary syndrome (ACS) patients and to compare the level of small dense LDL (sdLDL) to other markers used in cardiovascular risk prediction. Methods: A total of 205 ACS patients and 100 healthy control subjects were enrolled. LDL...

Background Alzheimer’s disease (AD) is the most common form of dementia with the symptoms gradually worsening over the years. However, the driving pathological processes occur well before the appearance of symptoms. AD patients display signs of systemic inflammation, suggesting that it could precede the well-established AD hallmarks. We recently sh...

Recent observations from clinical trials using monoclonal antibodies against Aβ seem to suggest that Aβ-targeting is modestly effective and not sufficiently based on an effective challenge of the role of Aβ from physiological to pathological. After an accelerated approval procedure for aducanumab, and more recently lecanemab, their efficacy and saf...

We have shown before that at least one intracellular proteolytic system seems to be at least as abundant in the peripheral blood lymphocytes of centenarians as in the same cells of young individuals (with the cells of the elderly population showing a significant dip compared to both young and centenarian cohorts). Despite scarce published data, in...

Arterial inflammation is an indicator of atheromatous plaque vulnerability to detach and to obstruct blood vessels in the heart or in the brain thus causing heart attack or stroke. To date, it is difficult to predict the plaque vulnerability. This study was aimed to assess the behavior of 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18...

In this commentary, we offer an overview of the several environmental and metabolic factors that have been identified as contributing to the development of Alzheimer’s disease (AD). Many of these factors involve extracranial organ systems including immune system dysfunction accompanied by neuroinflammation (inflammaging), gastrointestinal dysbiosis...

Defined as, “stereotype, prejudice, and discrimination directly towards people because of their age”, ageism may contribute to adverse health outcomes, accelerate aging process, and increase the burden on health and social services. Little is known about the ageism impact on biological aging. Secondary analysis of the American Health and Retirement...

This paper will update care providers on the clinical and scientific aspects of frailty which affects an increasing proportion of older people living with HIV (PLWH). The successful use of combination antiretroviral therapy has improved long-term survival in PLWH. This has increased the proportion of PLWH older than 50 to more than 50% of the HIV p...

Background Sarcopenia is common among older individuals with and without type 2 diabetes mellitus (T2DM). There are conflicting evidence in support of the role of insulin in the development of age-related and T2DM-related sarcopenia. We investigated the relationships between the levels of fasting insulin and other blood biomarkers related to insuli...

Background Unravelling the mystery of Alzheimer’s disease (AD) requires urgent resolution given the worldwide increase of the aging population. There is a growing concern that the current leading AD hypothesis, the amyloid cascade hypothesis, does not stand up to validation with respect to emerging new data. Indeed, several paradoxes are being disc...

Food scientists have studied the many health benefits of polyphenols against pernicious human diseases. Evidence from scientific studies has shown that earlier healthy lifestyle changes, particularly in nutrition patterns, can reduce the burden of age-related diseases. In this context, a large number of plant-derived components belonging to the cla...

Traditionally, the immune system is understood to be divided into discrete cell types that are identified via surface markers. While some cell type distinctions are no doubt discrete, others may in fact vary on a continum, and even within discrete types, differences in surface marker abundance could have functional implications. Here we propose a n...

Having made substantial progress understanding molecules, cells, genes and pathways, aging biology research is now moving toward integration of these parts, attempting to understand how their joint dynamics may contribute to aging. Such a shift of perspective requires the adoption of a formal complex systems framework, a transition being facilitate...

Background: The goal of this work was to measure artery inflammation in aged volunteers with atherosclerosis using computed tomography (CT) and positron emission tomography (PET) with 18F-FDG. The artery plaques are composed of lipid rich fibrous tissue and foamy macrophages and are the most vulnerable for detachment. Such plaques can be differenti...

Critical transition theory suggests that complex systems should experience increased temporal variability just before abrupt state changes. We tested this hypothesis in 763 patients on long-term hemodialysis, using 11 biomarkers collected every two weeks and all-cause mortality as a proxy for critical transitions. We find that variability – measure...

Organismal ageing is associated with many physiological changes, including differences in the immune system of most animals. These differences are often considered to be a key cause of age-associated diseases as well as decreased vaccine responses in humans. The most often cited vaccine failure is seasonal influenza, but, while it is usually the ca...

Ageing is associated with modified function of both innate and adaptive immunity. It is believed that changes occurring in ageing immune system are responsible for increased severity and deadliness of COVID-19 in the elderly. Although supported by statistics and epidemiology, these finding do not compute at the mechanistic level as depending solely...

Ketones, the brain's alternative fuel to glucose, bypass the brain glucose deficit and improve cognition in mild cognitive impairment (MCI). Our goal was to assess the impact of a 6-month ketogenic intervention on the functional connectivity within eight major brain resting-state networks, and its possible relationship to improved cognitive outcome...

Traditionally, the immune system is understood to be divided into discrete cell types that are identified via surface markers. While some cell type distinctions are no doubt discrete, others may in fact vary on a continuum, and even within discrete types, differences in surface marker abundance could have functional implications. Here we propose a...

Unravelling the mystery of Alzheimer Disease (AD) requires urgent resolution given the worldwide increase of the aging population. There is a growing concern that the current leading AD hypothesis, the amyloid cascade hypothesis, does not stand up to validation with respect to emerging new data. Indeed, several paradoxes are being discussed in the...

Introduction: There is empirical evidence that cardiovascular risk factors and vascular pathology contribute to cognitive impairment and dementia. Methods: We profiled cardiometabolic and vascular disease (CMVD) and CMVD burden in community-living older adults in the Singapore Longitudinal Ageing Study cohort and examined the association of CMVD...

Alzheimer’s disease (AD) is the most frequent cause of dementia due to neurodegeneration. It is stated that the most important risk factor for the late onset AD development is age. AD develops during decades and appears most of the time after 65 years of age. Even though its incidence is increasing with age but not all the centenarians are sufferin...

Aging is associated with numerous physiological changes, including those affecting the immune response. It is now well accepted that both the innate and the adaptive immune responses are changing with aging. The phenotypes and the functions of the immune cells are impacted at various degrees with aging. Collectively these changes are called immunos...

Background The capacity of ketones to improve cognition in mild cognitive impairment (MCI) may depend on ApoE4 status. In the BENEFIC RCT (NCT02551419), improvement in three cognitive domains was directly related to ketones from medium chain triglyceride (kMCT) improving global brain energy status. Post‐kMCT, ketone uptake increased 2.9‐fold in tot...

Background Ketones, the brain’s alternative fuel to glucose, bypass the brain glucose deficit in mild cognitive impairment (MCI). The BENEFIC trial conducted in MCI showed improved measures of cognition in multiple domains after a 6‐month ketogenic intervention [Fortier et al . 2019]. Functional connectivity in the dorsal‐attention network (DAN) de...

Sepsis is a prevalent life-threatening condition related to a systemic infection, and with unresolved issues including refractory septic shock and organ failures. Endogenously released catecholamines are often inefficient to maintain blood pressure, and low reactivity to exogenous catecholamines with risk of sympathetic overstimulation is well docu...

Introduction: White matter (WM) energy supply is crucial for axonal function and myelin maintenance. An exogenous source of ketones, the brain's alternative fuel to glucose, bypasses the brain's glucose-specific energy deficit and improves cognitive outcomes in mild cognitive impairment (MCI). How an additional supply of ketones affects glucose or...

The inflammaging concept was introduced in 2000 by Prof. Franceschi. This was an evolutionary or rather a revolutionary conceptualization of the immune changes in response to a lifelong stress. This conceptualization permitted to consider the lifelong proinflammatory process as an adaptation which could eventually lead to either beneficial or detri...

Natural antioxidants products are widely distributed in food and medicinal plants. These natural antioxidants, especially polyphenols, exhibit a wide range of biological activities including anti-cancer, anti-inflammatory, and anti-atherosclerosis activities. Pomegranate (Punica granatum L.) is a rich source of polyphenolic components. The purpose...

Background Growing evidence supports that receptor for advanced glycation end products (RAGE) and glyoxalase-1 (GLO-1) are implicated in the pathophysiology of Alzheimer’s disease (AD). Extracellular vesicles (EVs) are nanovesicles secreted by almost all cell types, contribute to cellular communication, and are implicated in AD pathology. Recently,...

High-density lipoproteins (HDL) maintain cholesterol homeostasis through the role they play in regulating reverse cholesterol transport (RCT), a process by which excess cholesterol is transported back to the liver for elimination. However, RCT can be altered in the presence of cardiovascular risk factors, such as aging, which contributes to the inc...

Background Alzheimer’s disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of per...

Critical transition theory suggests that complex systems should experience increased temporal variability just before abrupt change, such as increases in clinical biomarker variability before mortality. We tested this in the context of hemodialysis using 11 clinical biomarkers measured every two weeks in 763 patients over 2496 patient-years. We sho...

Alzheimer’s disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of am...

The anti-atherogenic activity of HDL is mainly due to their capacity to mediate reverse cholesterol transport (RCT). However, it is not clear to what extent this activity is affected by aging or pro-atherogenic conditions. Three and 24-month-old C57Bl/6 mice were fed an atherogenic diet (high fat, high cholesterol) for 12 weeks. The aged mice displ...

Background: Age-related changes in biological processes such as physiological dysregulation (the progressive loss of homeostatic capacity) vary considerably among older adults and may influence health profiles in late life. These differences could be related, at least in part, to the impact of intrinsic and extrinsic factors such as sex and physic...

INTRODUCTION: White matter (WM) energy supply is crucial for axonal function and myelin maintenance. Providing ketones, the brain s alternative fuel to glucose, is a therapeutic strategy to bypass the brain s glucose-specific energy deficit in mild cognitive impairment (MCI). How an additional supply of ketones affects glucose or ketone uptake in s...

There is an increasingly widespread use of biomarkers in network physiology to evaluate an organism’s physiological state. A recent study showed that albumin variability increases before death in chronic hemodialysis patients. We hypothesized that a multivariate statistical approach would better allow us to capture signals of impending physiologica...

Objectives Cancer-related fatigue (CRF) is the most debilitating side effect occurring with cancer treatment accumulation. Although combining aerobic and resistance exercise is an effective strategy to counteract this side effect, there is a paucity of studies performed with older patients even if this is the most affected population. Hence, the ob...

Background Lifelong accumulation of latent or persistent or repeated infections may be a contributing factor to the deterioration of physical and cognitive function associated with functional ageing, but the evidence is limited and the biological underpinnings are unclear. Methods We profiled the seropositivity for common viral, bacterial and plas...

All aspects of each protein existence in the eukaryotic cells, starting from the pre-translation events, through translation, multiple different post-translational modifications, functional life and eventual proteostatic removal after loss of functionality and changes in physico-chemical properties, can be collectively called the proteodynamics. Wi...

Purpose of review: Cancer is a disease of older adults, where fitness and frailty are a continuum. This aspect poses unique challenges to the management of cancer in this population. In this article, we review the biological aspects influencing the efficacy and safety of systemic anticancer treatments. Recent findings: The organ function decline...

One of the features that characterize both aging and aging-related diseases is the development and progression of a chronic, low-grade, and therefore for a long time subclinical, inflammatory state called inflammaging. Although the progression of inflammaging is currently recognized as one of the main driving forces of aging and one of the main ris...

This entry/chapter is providing the reader with up-to-date information on properties, functions and methods of studying of human natural killer (NK) cells. Their roles in health and disease (especially as one of the main means of defense against malignant (cancer) and virus-infected cells) are elaborated upon, as are their phenotypic and functional...

Living systems are subject to the arrow of time; from birth, they undergo complex transformations (self-organization) in a constant battle for survival, but inevitably ageing and disease trap them to death. Can ageing be understood and eventually reversed? What tools can be employed to further our understanding of ageing? The present article is an...

Background Ketones can partially substitute for glucose as a brain fuel and may be beneficial for cognition in older people. The objective of the randomized, placebo‐controlled Benefic Trial (NCT02551419) was to assess whether counteracting the brain energy (glucose) deficit with a ketogenic medium chain triglyceride (kMCT) supplement could improve...

Background Advanced glycation end‐products (AGEs), their precursors methylglyoxal (MG), glyoxal (GO) and their receptors RAGEs are known to be involved in the pathophysiology of Alzheimer’s disease (AD). The aim of our study was to evidence the presence of RAGEs and glyoxalase‐1 (GLO‐1), the main enzyme involved in the degradation of MG, in the cir...

Introduction Mild cognitive impairment (MCI) is often accompanied by metabolic abnormalities and inflammation that might play a role in the development of cognitive impairment. The use of ketogenic medium-chain triglycerides (kMCT) to improve cognition in this population has shown promising results but remains controversial because of the potential...

Human evidence for the role of continuous antigenic stimulation from persistent latent infections in frailty is limited. We conducted a nested case-control study (99 deceased and 43 survivors) of participants aged 55 and above in a longitudinal ageing cohort followed up from 2003 to 2017. Using blood samples and baseline data collected in 2003-2004...

Le trouble cognitif léger (TCL) est une condition se situant entre le vieillis- sement normal et les troubles neurocognitifs majeurs comme la maladie d’Al- zheimer (MA). Les personnes ayant un TCL présentent de légers problèmes pour certaines fonctions mentales, sans pour autant que cela nuise à leur autonomie. Comparativement aux personnes du mê...

Background Fried’s Phenotype Model of Frailty (PMF) postulates that frailty is a syndrome. Features of a syndrome are a heterogeneous population that can be split into at least two classes, those presenting and those not presenting the syndrome. Syndromes are characterized by a specific mixture of signs and symptoms which increase in prevalence, fr...

Introduction: Counteracting impaired brain glucose metabolism with ketones may improve cognition in mild cognitive impairment (MCI). Methods: Cognition, plasma ketone response, and metabolic profile were assessed before and 6 months after supplementation with a ketogenic drink containing medium chain triglyceride (ketogenic medium chain triglyce...

Alterations in the immune system with aging are considered to underlie many age-related diseases. However, many elderly individuals remain healthy until even a very advanced age. There is also an increase in numbers of centenarians and their apparent fitness. We should therefore change our unilaterally detrimental consideration of age-related immun...

Are diseases caused by aging? What are the mechanisms of aging? Do all species age? These hotly debated questions revolve around a unitary definition of aging. Because we use the word "aging" so frequently, both colloquially and scientifically, we rarely pause to consider whether this word maps to an underlying biological phenomenon, or whether it...