Tamas Kiss

• M.D.; Ph.D.
• PostDoc Position at Semmelweis University

Aging is associated with a progressive decline in circulating insulin-like growth factor- 1 (IGF- 1) levels in humans, which has been implicated in the pathogenesis of sarcopenia. IGF- 1 is an anabolic hormone that plays a dual role in maintaining skeletal muscle health, acting both directly on muscle fibers to promote growth and indirectly by supp...

With advancing age, neurovascular dysfunction manifests as impaired neurovascular coupling (NVC), microvascular rarefaction, and blood–brain barrier (BBB) disruption, contributing to vascular cognitive impairment (VCI). Our previous research established a causal link between vascular senescence induced cerebromicrovascular dysfunction and cognitive...

Vascular cognitive impairment (VCI) is a leading cause of age-related cognitive decline, driven by cerebrovascular dysfunction and cerebral small vessel disease (CSVD). Emerging evidence suggests that cerebromicrovascular endothelial senescence plays an important role in the pathogenesis of VCI by promoting cerebral blood flow dysregulation, neurov...

Chemotherapy-induced cognitive impairment (CICI), commonly referred to as “chemobrain,” is a frequent and debilitating side effect experienced by cancer survivors treated with paclitaxel (PTX). Preclinical models have shown that PTX promotes cerebromicrovascular endothelial cell senescence, leading to chronic blood–brain barrier (BBB) disruption an...

High-fat diets (HFDs) have pervaded modern dietary habits, characterized by their excessive saturated fat content and low nutritional value. Epidemiological studies have compellingly linked HFD consumption to obesity and the development of type 2 diabetes mellitus. Moreover, the synergistic interplay of HFD, obesity, and diabetes expedites the agin...

Cerebrovascular fragility and cerebral microhemorrhages (CMH) contribute to age-related cognitive impairment, mobility defects, and vascular cognitive impairment and dementia, impairing healthspan and reducing quality of life in the elderly. Insulin-like growth factor 1 (IGF-1) is a key vasoprotective growth factor that is reduced during aging. Cir...

Introduction Cerebrovascular pathologies contribute to cognitive decline during aging, leading to vascular cognitive impairment and dementia (VCID). Levels of circulating insulin-like growth factor 1 (IGF-1), a vasoprotective hormone, decrease during aging. Decreased circulating IGF-1 in animal models leads to the development of VCID-like symptoms,...

Hair graying, also known as canities or achromotrichia, is a natural phenomenon associated with aging and is influenced by external factors such as stress, environmental toxicants, and radiation exposure. Understanding the mechanisms underlying hair graying is an ideal approach for developing interventions to prevent or reverse age-related changes...

Whole brain irradiation (WBI), also known as whole brain radiation therapy (WBRT), is a well-established treatment for multiple brain metastases and as a preventive measure to reduce the risk of recurrence after surgical removal of a cerebral metastasis. However, WBI has been found to lead to a gradual decline in neurocognitive function in approxim...

Astrocytic dysfunction is central to age-related neurodegenerative diseases. However, the mechanisms leading to astrocytic dysfunction are not well understood. We identify that among the diverse cellular constituents of the brain, murine and human astrocytes are enriched in the expression of CBS. Depleting CBS in astrocytes causes mitochondrial dys...

Whole brain irradiation (WBI), a commonly employed therapy for multiple brain metastases and as a prophylactic measure after cerebral metastasis resection, is associated with a progressive decline in neurocognitive function, significantly impacting the quality of life for approximately half of the surviving patients. Recent preclinical investigatio...

Microglia cells, the immune cells residing in the brain, express immune regulatory molecules that have a central role in the manifestation of age-related brain characteristics. Our hypothesis suggests that galectin-1, an anti-inflammatory member of the beta-galactoside-binding lectin family, regulates microglia and neuroinflammation in the aging br...

Background: Epidemiological data shows modifiable risk factors have a decisive role in the development of cardiovascular diseases. Previously, these modifiable risk factors, including obesity, were mostly present in the adult population, however in the last decades they have also become prevalent among children. According to recently published data...

Chemotherapy-induced cognitive impairment ("chemobrain") is a frequent side-effect in cancer survivors treated with paclitaxel (PTX). The mechanisms responsible for PTX-induced cognitive impairment remain obscure, and there are no effective treatments or prevention strategies. Here, we test the hypothesis that PTX induces endothelial senescence, wh...

At the 50th AGE meeting in San Antonio, I presented our recent work on the role of circulating factors in vascular aging, with an emphasis on the changes in function and transcriptome of the macrovasculature exposed to circulating factors enriched in young and aged blood.

Vascular aging has a central role in the pathogenesis of cardiovascular diseases contributing to increased mortality of older adults. There is increasing evidence that, in addition to the documented role of cell-autonomous mechanisms of aging, cell-nonautonomous mechanisms also play a critical role in the regulation of vascular aging processes. Our...

There is strong evidence that aging is associated with an increased presence of senescent cells in the brain. The finding that treatment with senolytic drugs improves cognitive performance of aged laboratory mice suggests that increased cellular senescence is causally linked to age-related cognitive decline. The relationship between senescent cells...

Cerebral microhemorrhages (CMHs; microbleeds), which are small focal intracerebral hemorrhages, importantly contribute to the pathogenesis of cognitive decline and dementia in older adults. Although recently it has been increasingly recognized that the venous side of the cerebral circulation likely plays a fundamental role in the pathogenesis of a...

Moment-to-moment adjustment of regional cerebral blood flow to neuronal activity via neurovascular coupling (NVC or “functional hyperemia”) has a critical role in maintenance of healthy cognitive function. Aging-induced impairment of NVC responses importantly contributes to age-related cognitive decline. Advanced aging is associated with increased...

Aging is associated with a significant deficiency in circulating insulin-like growth factor-1 (IGF-1), which has an important role in the pathogenesis of age-related vascular cognitive impairment (VCI). Impairment of moment-to-moment adjustment of regional cerebral blood flow via neurovascular coupling (NVC) importantly contributes to VCI. Previous...

Age-related blood-brain barrier disruption and cerebromicrovascular rarefaction contribute importantly to the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Recent advances in geroscience research enable development of novel interventions to reverse age-related alterations of the cerebral microc...

Over two thirds of individuals aged 65 and older are obese or overweight in the United States. Epidemiological data show an association between the degree of adiposity and cognitive dysfunction in the elderly. In this review, the pathophysiological roles of microvascular mechanisms, including impaired endothelial function and neurovascular coupling...

Clinical studies show that cerebral amyloid angiopathy (CAA) associated with Alzheimer’s disease (AD) and arterial hypertension are independent risk factors for cerebral microhemorrhages (CMHs). To test the hypothesis that amyloid pathology and hypertension interact to promote the development of CMHs, we induced hypertension in the Tg2576 mouse mod...

Adjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling (NVC) plays an important role in the maintenance of healthy cognitive function. Strong evidence demonstrates that age‐related cerebromicrovascular endothelial dysfunction and consequential impairment of NVC responses contribute importantly to cognitive decline....

Cognitive impairment is one of the most common co‐occurring chronic conditions among elderly heart failure patients (incidence: up to ~ 80%); however, the underlying mechanisms are not completely understood. It is hypothesized that in addition to decreased cardiac output, increases in central‐and consequentially, cerebral‐venous pressure (backward...

Adjustment of cerebral blood flow (CBF) to the increased oxygen and nutrient demands of active brain regions via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In advanced age, cerebromicrovascular oxidative stress and endothelial dysfunction impair neurovascular coupling, contributing to age‐relate...

Understanding molecular mechanisms involved in vascular aging is essential to develop novel interventional strategies for treatment and prevention of age‐related vascular pathologies. Recent studies provide critical evidence that vascular aging is characterized by NAD+ depletion. Importantly, in aged mice, restoration of cellular NAD+ levels by tre...

Age‐related impairment of angiogenesis likely has a critical role in cerebromicrovascular rarefaction and development of vascular cognitive impairment and dementia (VCID) in the elderly. Recently, we demonstrated that aging is associated with NAD+ depletion in the vasculature and that administration of NAD+ precursors exerts potent anti‐aging vascu...

Introduction Normal brain function requires appropriate provision of oxygen, glucose, and other nutrients. This requirement is fulfilled through continuous adjustment of cerebral blood flow (CBF), the process also known as neurovascular coupling (NVC). Therefore, impairment of the resting CBF or impairment of NVC in the brain may be responsible for...

Whole brain irradiation (WBI, also known as whole brain radiation therapy or WBRT) is a mainstream therapy for patients with identifiable brain metastases and as a prophylaxis for microscopic malignancies. WBI accelerates brain aging, causing progressive cognitive dysfunction in ~50% of surviving patients, thus compromising quality of life. The mec...

Adjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In aging increased oxidative stress and cerebromicrovascular endothelial dysfunction impair NVC, contributing to cognitive decline. There is increasing evidence showing that a decrease in...

Age-related phenotypic changes of cerebromicrovascular endothelial cells lead to dysregulation of cerebral blood flow and blood-brain barrier disruption, promoting the pathogenesis of vascular cognitive impairment (VCI). In recent years, endothelial cell senescence has emerged as a potential mechanism contributing to microvascular pathologies openi...

Aging-induced functional and phenotypic alterations of the vasculature (e.g., endothelial dysfunction, oxidative stress) have a central role in morbidity and mortality of older adults. It has become apparent in recent years that cell autonomous mechanisms alone are inadequate to explain all aspects of vascular aging. The present study was designed...

Aging is a crucial cause of cognitive decline and a major risk factor for Alzheimer’s disease (AD); however, AD’s underlying molecular mechanisms remain unclear. Recently, tetraspanins have emerged as important modulators of synaptic function and memory. We demonstrate that the level of tetraspanin CD82 is upregulated in the brains of AD patients a...

Aging-induced structural and functional alterations of the neurovascular unit lead to impairment of neurovascular coupling responses, dysregulation of cerebral blood flow, and increased neuroinflammation, all of which contribute importantly to the pathogenesis of age-related vascular cognitive impairment (VCI). There is increasing evidence showing...

Whole brain irradiation (WBI, also known as whole brain radiation therapy or WBRT) is a mainstream therapy for patients with identifiable brain metastases and as a prophylaxis for microscopic malignancies. WBI accelerates brain aging, causing progressive cognitive dysfunction in ~ 50% of surviving patients, thus compromising quality of life. The me...

Cognitive impairment is one of the most common co-occurring chronic conditions among elderly heart failure patients (incidence: up to ~ 80%); however, the underlying mechanisms are not completely understood. It is hypothesized that in addition to decreased cardiac output, increases in central—and consequentially, cerebral—venous pressure (backward...

Adjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling (NVC) plays an important role in the maintenance of healthy cognitive function. Strong evidence demonstrates that age-related cerebromicrovascular endothelial dysfunction and consequential impairment of NVC responses contribute importantly to cognitive decline....

Preclinical studies provide strong evidence that age-related impairment of neurovascular coupling (NVC) plays a causal role in the pathogenesis of vascular cognitive impairment (VCI). NVC is a critical homeostatic mechanism in the brain, responsible for adjustment of local cerebral blood flow to the energetic needs of the active neuronal tissue. Re...

Aging is associated with increased oxidative stress in vascular endothelial and smooth muscle cells, which contribute to the development of a wide range of diseases affecting the circulatory system in older adults. There is growing evidence that in addition to increased production of reactive oxygen species (ROS), aging critically impairs pathways...

Adjustment of cerebral blood flow (CBF) to the increased oxygen and nutrient demands of active brain regions via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In advanced age, cerebromicrovascular oxidative stress and endothelial dysfunction impair neurovascular coupling, contributing to age-relate...

Understanding molecular mechanisms involved in vascular aging is essential to develop novel interventional strategies for treatment and prevention of age-related vascular pathologies. Recent studies provide critical evidence that vascular aging is characterized by NAD+ depletion. Importantly, in aged mice, restoration of cellular NAD+ levels by tre...

Age-related impairment of angiogenesis likely has a critical role in cerebromicrovascular rarefaction and development of vascular cognitive impairment and dementia (VCID) in the elderly. Recently, we demonstrated that aging is associated with NAD⁺ depletion in the vasculature and that administration of NAD⁺ precursors exerts potent anti-aging vascu...

Disruptions in growth hormone/insulin-like growth factor-1 (GH/IGF-1) signaling have been linked to improved longevity in mice and humans. Nevertheless, while IGF-1 levels are associated with increased cancer risk, they have been paradoxically implicated with protection from other age-related conditions, particularly in the brain, suggesting that s...

Preclinical studies demonstrate that generalized endothelial cell dysfunction and microvascular impairment are potentially reversible causes of age-related vascular cognitive impairment and dementia (VCID). The present study was designed to test the hypothesis that severity of age-related macro- and microvascular dysfunction measured in the periphe...

Adjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In aging increased oxidative stress and cerebromicrovascular endothelial dysfunction impair NVC, contributing to cognitive decline. There is increasing evidence showing that a decrease in...

Circulating levels of IGF‐1 decline during aging in humans, which significantly increases the risk for cardiovascular diseases and promotes cerebromicrovascular impairment. To test the hypothesis that impaired IGF‐1 input to endothelial cells promote aging‐like microvascular dysfunction, we utilized a novel mouse model: Igfr1 f/f VE‐Cadherin‐Cre mi...

Background It is predicted that by the year 2030 every 5 th American will be >65 years of age. There is growing importance to understand age‐associated changes that lead to vascular cognitive impairment (CI) and dementia. Normal brain function is critically dependent on moment‐to‐moment adjustment of cerebral blood flow (CBF) to neuronal activity,...

BACKGROUND Age‐related vascular cognitive impairment and dementia (VCID), defined as cognitive decline caused by cerebromicrovascular pathologies, is a major public health issue that affects >10 million individuals aged 65 and older in the US with annual healthcare costs totaling >$100 billion. Aging is a major risk factor for the development of VC...

Recent studies demonstrate that aging exacerbates hypertension‐induced cognitive decline, but the specific age‐related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function. To determine whether aging exacerbates hypertension‐i...

Age‐related gait dysfunction and balance disorders are a major cause of falls and injury in the elderly population. Epidemiological studies have shown that disturbances in gait coordination which manifest with age are associated with increased morbidity and mortality, impaired cognitive capacity, as well as reduced level of function and loss of ind...

Insulin‐like growth factor 1 (IGF‐1) exerts multifaceted protective effects on the cerebral microcirculation and age‐related reduction of circulating IGF‐1 levels is known to promote cognitive decline. Astrocyte‐mediated neurovascular coupling (NVC), which adjusts cerebral blood flow to increased energy requirements of activated neurons, plays a cr...

Previous studies demonstrate that obesity promotes cognitive impairment due to, at least in part, its deleterious effects on the cerebral microvasculature. Importantly, the effects of obesity are exacerbated in aging, but the underlying mechanisms remain elusive. Nuclear factor erythroid 2‐related factor (Nrf2) is a master transcriptional factor th...

Aging‐induced pro‐inflammatory phenotypic alterations of the cerebral vasculature critically contribute to the pathogenesis of vascular cognitive impairment. Cellular senescence is a fundamental aging process that promote inflammation, however, its role in cerebrovascular aging remains unexplored. The present study was undertaken to test the hypoth...

Age-related alterations in endothelium and the resulting vascular dysfunction critically contribute to a range of pathological conditions associated with old age. To develop therapies rationally that improve vascular health and thereby increase health span and life span in older adults, it will be essential to understand the cellular and molecular...

There has been an increasing appreciation of the role of vascular contributions to cognitive impairment and dementia (VCID) associated with old age. Strong preclinical and translational evidence links age-related dysfunction and structural alterations of the cerebral arteries, arterioles, and capillaries to the pathogenesis of many types of dementi...

Aging-induced pro-inflammatory phenotypic alterations of the cerebral vasculature critically contribute to the pathogenesis of vascular cognitive impairment. Cellular senescence is a fundamental aging process that promotes inflammation; however, its role in cerebrovascular aging remains unexplored. The present study was undertaken to test the hypot...

Age-related gait dysfunction and balance disorders are a major cause of falls and injury in the elderly population. Epidemiological studies have shown that disturbances in gait coordination which manifest with age are associated with increased morbidity and mortality, impaired cognitive capacity, as well as reduced level of function and loss of ind...

Moment‐to‐moment adjustment of cerebral blood flow (CBF) via neurovascular coupling has a critical role in maintenance of healthy cognitive function. Previous studies demonstrate that obesity promotes cognitive impairment due to, at least in part, its deleterious effects on neurovascular coupling. Importantly, the effects of obesity are exacerbated...

Clinical and experimental studies show that age-related decline in circulating insulin-like growth factor-1 (IGF-1) levels promotes the pathogenesis of intracerebral hemorrhages, which critically contribute to the development of vascular cognitive impairment and disability in older adults. Yet, the mechanisms by which IGF-1 deficiency compromises s...

Obesity is one of the major risk factors for cardiovascular diseases and its prevalence is increasing in all age groups, with the biggest impact observed in middle-aged and older adults. A critical mechanism by which obesity promotes vascular pathologies in these patients involves impairment of endothelial function. While endothelial dysfunction in...

There is strong evidence that obesity has deleterious effects on cognitive function of older adults. Previous preclinical studies demonstrate that obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood brain barrier disruption, promoting neuroinflammation and oxidative stress. To test the hypothesis...

Ageing is the main risk factor for the development of cardiovascular diseases. A central mechanism by which ageing promotes vascular pathologies is compromising endothelial health. The age-related attenuation of endothelium-dependent dilator responses (endothelial dysfunction) associated with impairment of angiogenic processes and the subsequent pa...

Supplementary material Supplemental Figure 1. Immunoblot and protein gel images show the abundance of Nrf2 proteins in young, old and old-Nrf2-/-. Retinal pigment epithelial cells were treated with MG132 for 0 and 4 h for identification of Nrf2. n = 4. *p < 0.05 old vs. old-Nrf2-/-. Supplemental Table 1. Gastrocnemius muscle protein abundances of a...

There is correlative evidence that impaired cerebral blood flow (CBF) regulation, in addition to promoting cognitive impairment, is also associated with alterations in gait and development of falls in elderly people. CBF is adjusted to neuronal activity via neurovascular coupling (NVC) and this mechanism becomes progressively impaired with age. To...

Insulin‐like growth factor 1 (IGF‐1) exerts multifaceted protective effects on the cerebral microcirculation and age‐related reduction of circulating IGF‐1 levels is known to promote cognitive decline. Astrocyte‐mediated neurovascular coupling (NVC), which adjusts cerebral blood flow to increased energy requirements of activated neurons, plays a cr...

There is strong evidence that obesity has deleterious effects on cognitive function of older adults. Previous preclinical studies demonstrate that obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood brain barrier disruption, promoting neuroinflammation and oxidative stress. To test the hypothesis...

Clinical and experimental studies show that age‐related decline in circulating IGF‐1 levels promotes the pathogenesis of intracerebral hemorrhages, which critically contribute to the development of vascular cognitive impairment and disability in older adults. Yet, the mechanisms by which IGF‐1 deficiency compromises structural integrity of the cere...

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There is correlative evidence that impaired cerebral blood flow (CBF) regulation, in addition to promoting cognitive impairment, is also associated with alterations in gait and development of falls in elderly people. CBF is adjusted to neuronal activity via neurovascular coupling (NVC) and this mechanism becomes progressively impaired with age. To...

Obesity has deleterious effects on cognitive function in the elderly. In mice, aging exacerbates obesity-induced oxidative stress, microvascular dysfunction, blood-brain barrier (BBB) disruption and neuroinflammation, which compromise cognitive health. However, the specific mechanisms through which aging and obesity interact to remain elusive. Prev...

Connective tissue growth factor (CTGF, also known as CCN2) is a matricellular protein expressed in the vascular wall, which regulates diverse cellular functions including cell adhesion, matrix production, structural remodeling, angiogenesis, and cell proliferation and differentiation. CTGF is principally regulated at the level of transcription and...

Hypertension in the elderly substantially increases both the risk of vascular cognitive impairment (VCI) and Alzheimer’s disease (AD); however, the underlying mechanisms are not completely understood. This review discusses the effects of hypertension on structural and functional integrity of cerebral microcirculation, including hypertension-induced...

Increasing evidence from epidemiological, clinical, and experimental studies indicates that cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including both vascular cognitive impairment (VCI) and Alzheimer's disease. Vascular contributions to cognitive imp...

Whole brain irradiation (WBI) is a mainstream therapy for patients with both identifiable brain metastases and prophylaxis for microscopic malignancies. However, it also promotes accelerated senescence in healthy tissues and leads to progressive cognitive dysfunction in up to 50% of tumor patients surviving long term after treatment, due to γ-irrad...

Spreading depolarizations of long cumulative duration have been implicated in lesion development and progression in patients with stroke and traumatic brain injury. Spreading depolarizations evolve less likely in the aged brain, but it remains to be determined at what age the susceptibility to spreading depolarizations starts to decline, especially...