Advances and challenges in geroscience research: An update

Aging remains the most pervasive risk factor for a wide range of chronic diseases that afflict modern societies. In the United States alone, incidence of age-related diseases (e.g., cardiovascular disease, stroke, Alzheimer’s disease, vascular cognitive impairment and dementia, cancer, hypertension, type-2 diabetes, chronic obstructive pulmonary disease, and osteoarthritis) is on the rise, posing an unsustainable socioeconomic burden even for the most developed countries. Tackling each and every age-related disease alone is proving to be costly and ineffective. The emerging field of geroscience has posed itself as an interdisciplinary approach that aims to understand the relationship between the biology of aging and the pathophysiology of chronic age-related diseases. According to the geroscience concept, aging is the single major risk factor that underlies several age-related chronic diseases, and manipulation of cellular and systemic aging processes can delay the manifestation and/or severity of these age-related chronic pathologies. The goal of this endeavor is to achieve health improvements by preventing/delaying the pathogenesis of several age-related diseases simultaneously in the elderly population by targeting key cellular and molecular processes of aging instead of managing diseases of aging as they arise individually. In this review, we discuss recent advances in the field of geroscience, highlighting their implications for potential future therapeutic targets and the associated scientific challenges and opportunities that lay ahead

Ambulatory electrocardiography

The book is devoted to ambulatory ECG monitoring from technical issues to clinical use with examples of reports and interpretation of the obtained results. For students of medical faculties, functional diagnostics specialists, cardiologists, doctors of other specialties who use ambulatory electrocardiography in their work.Книга присвячена амбулаторному моніторингу ЕКГ від технічних питань до клінічного використання з прикладами звітів та інтерпретацією отриманих результатів. Для студентів медичних факультетів, спеціалістів з функціональної діагностики, кардіологів, лікарів інших спеціальностей, які використовують у своїй роботі амбулаторну електрокардіографію

Obesity-induced cognitive impairment in older adults: a microvascular perspective

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 responses, microvascular rarefaction, and blood-brain barrier disruption in the genesis of cognitive impairment in geriatric obesity are considered. The potential contribution of adipose-derived factors and fundamental cellular and molecular mechanisms of senescence to exacerbated obesity-induced cerebromicrovascular impairment and cognitive decline in aging are discussed

A CLINICAL CASE OF WEBER-CHRISTIAN DISEASE

A clinical case of elderly female patient diagnosed with Weber-Christian disease developed on the background of long standing chronic autoimmune thyroiditis with impaired function of the thyroid gland (hypothyroidism) and unstable hormonal status, after surgery (hysterectomy, oophorectomy)

Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures

The aging population worldwide is facing a significant increase in age-related non-communicable diseases, including cardiovascular and brain pathologies. This comprehensive review paper delves into the impact of the exposome, which encompasses the totality of environmental exposures, on unhealthy aging. It explores how environmental factors contribute to the acceleration of aging processes, increase biological age, and facilitate the development and progression of a wide range of age-associated diseases. The impact of environmental factors on cognitive health and the development of chronic age-related diseases affecting the cardiovascular system and central nervous system is discussed, with a specific focus on Alzheimer’s disease, Parkinson’s disease, stroke, small vessel disease, and vascular cognitive impairment (VCI). Aging is a major risk factor for these diseases. Their pathogenesis involves cellular and molecular mechanisms of aging such as increased oxidative stress, impaired mitochondrial function, DNA damage, and inflammation and is influenced by environmental factors. Environmental toxicants, including ambient particulate matter, pesticides, heavy metals, and organic solvents, have been identified as significant contributors to cardiovascular and brain aging disorders. These toxicants can inflict both macro- and microvascular damage and many of them can also cross the blood–brain barrier, inducing neurotoxic effects, neuroinflammation, and neuronal dysfunction. In conclusion, environmental factors play a critical role in modulating cardiovascular and brain aging. A deeper understanding of how environmental toxicants exacerbate aging processes and contribute to the pathogenesis of neurodegenerative diseases, VCI, and dementia is crucial for the development of preventive strategies and interventions to promote cardiovascular, cerebrovascular, and brain health. By mitigating exposure to harmful environmental factors and promoting healthy aging, we can strive to reduce the burden of age-related cardiovascular and brain pathologies in the aging population

Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice

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 NAD+ availability with age plays a critical role in a range of age-related cellular impairments but its role in impaired NVC responses remains unexplored. The present study was designed to test the hypothesis that restoring NAD+ concentration may exert beneficial effects on NVC responses in aging. To test this hypothesis 24-month-old C57BL/6 mice were treated with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, for 2 weeks. NVC was assessed by measuring CBF responses (laser Doppler flowmetry) evoked by contralateral whisker stimulation. We found that NVC responses were significantly impaired in aged mice. NMN supplementation rescued NVC responses by increasing endothelial NO-mediated vasodilation, which was associated with significantly improved spatial working memory and gait coordination. These findings are paralleled by the sirtuin-dependent protective effects of NMN on mitochondrial production of reactive oxygen species and mitochondrial bioenergetics in cultured cerebromicrovascular endothelial cells derived from aged animals. Thus, a decrease in NAD+ availability contributes to age-related cerebromicrovascular dysfunction, exacerbating cognitive decline. The cerebromicrovascular protective effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective interventions in patients at risk for vascular cognitive impairment (VCI)

Cerebrovascular responses to graded exercise in young healthy males and females

Although systemic sex‐specific differences in cardiovascular responses to exercise are well established, the comparison of sex‐specific cerebrovascular responses to exercise has gone under‐investigated especially, during high intensity exercise. Therefore, our purpose was to compare cerebrovascular responses in males and females throughout a graded exercise test (GXT). Twenty‐six participants (13 Females and 13 Males, 24 ± 4 yrs.) completed a GXT on a recumbent cycle ergometer consisting of 3‐min stages. Each sex completed 50W, 75W, 100W stages. Thereafter, power output increased 30W/stage for females and 40W/stage for males until participants were unable to maintain 60‐80 RPM. The final stage completed by the participant was considered maximum workload(Wmax). Respiratory gases (End‐tidal CO2, EtCO2), middle cerebral artery blood velocity (MCAv), heart rate (HR), non‐invasive mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) were continuously recorded on a breath‐by‐breath or beat‐by‐beat basis. Cerebral perfusion pressure, CPP = MAP (0. 7,355 distance from heart‐level to doppler probe) and cerebral vascular conductance index, CVCi = MCAv/CPP 100mmHg were calculated. The change from baseline (Δ) in MCAv was similar between the sexes during the GXT (p = .091, ωp2 = 0.05). However, ΔCPP (p < .001, ωp2 = 0.25) was greater in males at intensities ≥ 80% Wmax and ΔCVCi (p = .005, ωp2 = 0.15) was greater in females at 100% Wmax. Δ End‐tidal CO2 (ΔEtCO2) was not different between the sexes during exercise (p = .606, ωp2 = −0.03). These data suggest there are sex‐specific differences in cerebrovascular control, and these differences may only be identifiable at high and severe intensity exercise.Open Access fees paid for in whole or in part by the University of Oklahoma Libraries.Ye

TIME FOR RADICAL CHANGE OF UNIVERSAL MYOCARDIAL INFARCTION DEFINITION HAS ARRIVED YESTERDAY

In this manuscript, we discuss a previously introduced definition of the myocardial infarction (MI), and propose to redefine it so it is not limited just to “a necrosis in the setting of myocardial ischemia”, which we think is the case only in the deceased individuals that died during the first few hours from the MI onset, but to include a broader description of the acute aseptic coronarogenic inflammation of the cardiac muscle. We suggest that the outcome of the MI to a large extant depends on the synchronization of the necrotic and reparative processes and that their desynchronization ultimately results in the development of MI complications. A better understanding of the MI and the use of appropriate definition is warranted for a development of new therapeutic targets