scholarly journals The aging venous system: from varicosities to vascular cognitive impairment

GeroScience ◽  
2021 ◽  
Author(s):  
Andrea Ágnes Molnár ◽  
György László Nádasy ◽  
Gabriella Dörnyei ◽  
Bernadett Bettina Patai ◽  
Jordan Delfavero ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Molecular Mechanisms ◽  
Varicose Veins ◽  
Critical Role ◽  
Vascular Cognitive Impairment ◽  
Venous System ◽  
Potential Contribution ◽  
Age Related ◽  
Venous Diseases

Abstract Aging-induced pathological alterations of the circulatory system play a critical role in morbidity and mortality of older adults. While the importance of cellular and molecular mechanisms of arterial aging for increased cardiovascular risk in older adults is increasingly appreciated, aging processes of veins are much less studied and understood than those of arteries. In this review, age-related cellular and morphological alterations in the venous system are presented. Similarities and dissimilarities between arterial and venous aging are highlighted, and shared molecular mechanisms of arterial and venous aging are considered. The pathogenesis of venous diseases affecting older adults, including varicose veins, chronic venous insufficiency, and deep vein thrombosis, is discussed, and the potential contribution of venous pathologies to the onset of vascular cognitive impairment and neurodegenerative diseases is emphasized. It is our hope that a greater appreciation of the cellular and molecular processes of vascular aging will stimulate further investigation into strategies aimed at preventing or retarding age-related venous pathologies.

Molecular Mechanisms of Complement System Proteins and Matrix Metalloproteinases in the Pathogenesis of Age-Related Macular Degeneration

2019 ◽  
Vol 19 (10) ◽  
pp. 705-718 ◽  
Author(s):  
Naima Mansoor ◽  
Fazli Wahid ◽  
Maleeha Azam ◽  
Khadim Shah ◽  
Anneke I. den Hollander ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Macular Degeneration ◽  
Complement System ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Age Related Macular Degeneration ◽  
Genetic Changes ◽  
Complement System Proteins ◽  
Age Related ◽  
Common Genetic Variants

: Age-related macular degeneration (AMD) is an eye disorder affecting predominantly the older people above the age of 50 years in which the macular region of the retina deteriorates, resulting in the loss of central vision. The key factors associated with the pathogenesis of AMD are age, smoking, dietary, and genetic risk factors. There are few associated and plausible genes involved in AMD pathogenesis. Common genetic variants (with a minor allele frequency of >5% in the population) near the complement genes explain 40–60% of the heritability of AMD. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. Genetic changes in and around several complement system genes, including the CFH, contribute to the formation of drusen and progression of AMD. Similarly, Matrix metalloproteinases (MMPs) that are normally involved in tissue remodeling also play a critical role in the pathogenesis of AMD. MMPs are involved in the degradation of cell debris and lipid deposits beneath retina but with age their functions get affected and result in the drusen formation, succeeding to macular degeneration. In this review, AMD pathology, existing knowledge about the normal and pathological role of complement system proteins and MMPs in the eye is reviewed. The scattered data of complement system proteins, MMPs, drusenogenesis, and lipofusogenesis have been gathered and discussed in detail. This might add new dimensions to the understanding of molecular mechanisms of AMD pathophysiology and might help in finding new therapeutic options for AMD.

Elevated Inflammatory Markers and Arterial Stiffening Exacerbate Tau but Not Amyloid Pathology in Older Adults with Mild Cognitive Impairment

2021 ◽  
pp. 1-13
Author(s):  
Alexandra L. Clark ◽  
Alexandra J. Weigand ◽  
Kelsey R. Thomas ◽  
Seraphina K. Solders ◽  
Lisa Delano-Wood ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Inflammatory Markers ◽  
Memory Performance ◽  
Cognitive Testing ◽  
Interactive Effects ◽  
Protein Biomarkers ◽  
Age Related ◽  
T Tau

Background: Age-related cerebrovascular and neuroinflammatory processes have been independently identified as key mechanisms of Alzheimer’s disease (AD), although their interactive effects have yet to be fully examined. Objective: The current study examined 1) the influence of pulse pressure (PP) and inflammatory markers on AD protein levels and 2) links between protein biomarkers and cognitive function in older adults with and without mild cognitive impairment (MCI). Methods: This study included 218 ADNI (81 cognitively normal [CN], 137 MCI) participants who underwent lumbar punctures, apolipoprotein E (APOE) genotyping, and cognitive testing. Cerebrospinal (CSF) levels of eight pro-inflammatory markers were used to create an inflammation composite, and amyloid-beta 1–42 (Aβ 42), phosphorylated tau (p-tau), and total tau (t-tau) were quantified. Results: Multiple regression analyses controlling for age, education, and APOE ɛ4 genotype revealed significant PP x inflammation interactions for t-tau (B = 0.88, p = 0.01) and p-tau (B = 0.84, p = 0.02); higher inflammation was associated with higher levels of tau within the MCI group. However, within the CN group, analyses revealed a significant PP x inflammation interaction for Aβ 42 (B = –1.01, p = 0.02); greater inflammation was associated with higher levels of Aβ 42 (indicative of lower cerebral amyloid burden) in those with lower PP. Finally, higher levels of tau were associated with poorer memory performance within the MCI group only (p s <  0.05). Conclusion: PP and inflammation exert differential effects on AD CSF proteins and provide evidence that vascular risk is associated with greater AD pathology across our sample of CN and MCI older adults.

scholarly journals Polygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum

2020 ◽  
Author(s):  
Niccolo’ Tesi ◽  
Sven J van der Lee ◽  
Marc Hulsman ◽  
Iris E Jansen ◽  
Najada Stringa ◽  
...  
Keyword(s):  
Older Adults ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Risk Scores ◽  
Human Longevity ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Polygenic Risk ◽  
Age Related

Abstract Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevity-associated variants. Using a cohort of centenarians with maintained cognitive health (N = 343), a population-matched cohort of older adults from 5 cohorts (N = 2905), and summary statistics data from genome-wide association studies on parental longevity, we constructed a PRS including 330 variants that significantly discriminated between centenarians and older adults. This PRS was also associated with longer survival in an independent sample of younger individuals (p = .02), leading up to a 4-year difference in survival based on common genetic factors only. We show that this PRS was, in part, able to compensate for the deleterious effect of the APOE-ε4 allele. Using an integrative framework, we annotated the 330 variants included in this PRS by the genes they associate with. We find that they are enriched with genes associated with cellular differentiation, developmental processes, and cellular response to stress. Together, our results indicate that an extended human life span is, in part, the result of a constellation of variants each exerting small advantageous effects on aging-related biological mechanisms that maintain overall health and decrease the risk of age-related diseases.

scholarly journals Age-Related Changes in Molecular and Whole Muscle Function: Role of Fat Content?

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 141-141
Author(s):  
Joseph Gordon III ◽  
Nicholas Remillard ◽  
Chad Straight ◽  
Rajakumar Nagarajan ◽  
Bruce Damon ◽  
...  
Keyword(s):  
Older Adults ◽  
Molecular Mechanisms ◽  
Fat Content ◽  
Fat Deposition ◽  
Muscle Size ◽  
Type I ◽  
Contraction Velocity ◽  
Age Related ◽  
Whole Muscle ◽  
Age Related Changes

Abstract Decreases in muscle size and function are a general consequence of old age; the precise mechanisms of these changes remain unclear. Recent studies suggest that fat deposition in muscle may also contribute to dysfunction in older adults. Fat content was quantified in the quadriceps, and its effects on function in healthy young (21-45 y) and older (65-75 y) men and women (n=44) of comparable physical activity were compared. A subset of the young matched with the older group for muscle fat content were also examined. Peak fat-free whole muscle cross-sectional area (mCSA; cm2), volume (MV; cm3), fat content (fat fraction, FF; %), specific torque (Nm/mCSA) and peak contraction velocity (Nm∙s-1) were determined using fat-water magnetic resonance imaging and dynamometry (0-300□∙s-1). To examine potential molecular mechanisms of muscle weakness, vastus lateralis biopsies were obtained (n=31) and cross-bridge kinetics of type I and II fibers were determined. FF was higher in older adults than young (8.4±1.2% (SE), 7.6±1.4; p=0.03), while mCSA (48.9±10.4 vs. 64.2±17.3), MV (1536±532 vs. 2112±708), specific torque (2.6±0.4 vs. 3.2±0.4), and peak voluntary contraction velocity (422±20 vs. 441±23) were lower in older than young (p&lt;0.01). Type II fiber myosin attachment rate was slower and attachment time longer in older muscle (p&lt;0.017), providing a potential mechanism for the slowing of peak contraction velocity with age. Notably, differences at the whole muscle and molecular levels remained for the subset of young and older groups matched for FF, suggesting that fat deposition in muscle does not exacerbate age-related changes in function.

scholarly journals The Relationship Between Hearing Loss and Cognitive Impairment in a Chinese Elderly Population: The Baseline Analysis

2021 ◽  
Vol 15 ◽  
Author(s):  
Xinxing Fu ◽  
Bo Liu ◽  
Shuo Wang ◽  
Robert H. Eikelboom ◽  
Dona M. P. Jayakody
Keyword(s):  
Older Adults ◽  
Hearing Loss ◽  
Cognitive Impairment ◽  
Health Care Professionals ◽  
Spatial Working Memory ◽  
Depression Anxiety Stress Scale ◽  
Paired Associates ◽  
Multiple Stepwise Regression Analysis ◽  
Age Related ◽  
Age Related Hearing Loss

Objectives: The objective of the study was to investigate the association between untreated age-related hearing loss and cognitive impairment in Mandarin-speaking older adults living in China.Methods: Older adults (293; 111 males, M = 70.33 ± 4.90 years; 182 females, M = 69.02 ± 4.08 years) were recruited. All participants completed a pure tone audiometric hearing assessment, Hearing Impairment-Montreal Cognitive Assessment Test (HI-MoCA), and a computerized neuropsychology test battery (CANTAB). The Mandarin version of the De Jong Gierveld Loneliness Scale was used to measure the loneliness, and the Mandarin version of the 21-item Depression Anxiety Stress Scale (DASS-21) was used to measure the current severity of a range of symptoms common to depression, stress, and anxiety of the participants.Results: A multiple stepwise regression analysis showed that the average of four mid-frequency thresholds in the better ear was related to CANTAB Paired Associates Learning (β = 0.20, p = 0.002), and the global cognitive function score (HI-MoCA) (β = −0.25, p &lt; 0.001). The average of three high frequencies in the better ear was significantly associated with CANTAB Delayed Matching to Sample (β = −0.16, p = 0.008), and Spatial Working Memory (β = 0.17, p = 0.003).Conclusion: The results revealed a significant relationship between age-related hearing loss and cognitive impairment in Mandarin-speaking older adults. These research outcomes have clinical implications specifically for hearing health care professionals in China and other populations that speak a tonal language, especially when providing hearing rehabilitation.

Hemodynamics in Alzheimer’s Disease and Vascular Cognitive Impairment and Dementia

2020 ◽  
pp. 302-330
Author(s):  
Francis Cambronero ◽  
Angela L. Jefferson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cerebrovascular Disease ◽  
Vascular System ◽  
Clinical Symptoms ◽  
Vascular Dysfunction ◽  
Critical Role ◽  
Vascular Cognitive Impairment ◽  
Aging Adults

Hemodynamic impairment is a prominent feature in aging, vascular cognitive impairment and dementia, and Alzheimer’s disease, including patterned changes in cerebral blood flow (CBF) that can be detected prior to concomitant pathologies. These CBF abnormalities drive vascular dysfunction through a variety of biological pathways and ultimately contribute to cerebrovascular disease associated with cognitive impairment. Importantly, the co-existence of cerebrovascular disease and Alzheimer’s disease is exceedingly common and worsens the progression of clinical symptoms, likely through accelerating neurotoxic protein deposition and the loss of cerebrovascular integrity. Emerging evidence further suggests that the brain may be more susceptible to subclinical cardiovascular dysfunction in aging adults, particularly since the accumulation of cardiovascular risk factors over the lifespan creates a more vulnerable vascular system. Although age-associated CBF dysregulation has varied and complex origins, it undoubtedly serves a critical role in the early progression of neurodegenerative disease and may help explain the considerable overlap between the most common clinical dementias.

scholarly journals Obesity-induced Cognitive Impairment in Older Adults: a Microvascular Perspective

2020 ◽  
Author(s):  
Priya Balasubramanian ◽  
Tamas Kiss ◽  
Stefano Tarantini ◽  
Ádám Nyúl-Tóth ◽  
Chetan Ahire ◽  
...  
Keyword(s):  
United States ◽  
Cognitive Impairment ◽  
Molecular Mechanisms ◽  
Epidemiological Data ◽  
The Elderly ◽  
The United States ◽  
Potential Contribution ◽  
Blood Brain Barrier Disruption ◽  
Brain Barrier Disruption ◽  
Microvascular Rarefaction

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.

scholarly journals P0018GLOMERULAR ENDOTHELIAL CELL SENESCENCE DRIVES AGE-RELATED KIDNEY DISEASE THROUGH PAI-1

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Camille Cohen ◽  
Legoff Oceanc ◽  
Frederic Soysouvanh ◽  
Marine Tanou ◽  
Florence Vasseur ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Kidney Disease ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Accelerated Aging ◽  
Plasminogen Activator Inhibitor 1 ◽  
Histological Lesion ◽  
Glomerular Endothelial Cells ◽  
Age Related ◽  
Pai 1

Abstract Background and Aims In age-related chronic kidney disease (CKD), the most frequent histological lesion observed is glomerulosclerosis. The molecular mechanisms involved in this deterioration process are unclear, but cellular senescence might play a role. Method By combining several murine models of physiological and accelerated aging with transgenic animals and in vitro models, we discovered the role of endothelial senescence in the development of glomerular lesions. Results These senescent glomerular endothelial cells secreted several molecules, grouped under the senescence associated secretory phenotype (SASP) including the plasminogen activator inhibitor 1 (PAI-1). Specific deletion of PAI-1 in endothelial cells prevented the development of glomerulosclerosis during physiological and accelerated aging, by decreasing podocyte loss. In addition, we showed that PAI-1 mediates a detrimental endothelial-podocyte crosstalk, as incubation of podocytes by supernatant of senescent glomerular endothelial cells led to their detachment. Consistently, preincubation of the senescent supernatant with tiplaxtinin, a PAI-1 inhibitor, preserved podocytes. More importantly, we demonstrated that these data are relevant to humans. In fact, PAI-1 staining the day of the transplantation was predictive of kidney allograft dysfunction 12 months after transplantation from elderly donors. Conclusion In conclusion, our study uncovers the critical role played by endothelial senescence in the development of glomerulosclerosis during aging and identified PAI-1 as a novel promising biomarker for predicting kidney dysfunction in patients receiving a kidney from elderly donors.

Increased Aerobic Fitness Is Associated with Cortical Thickness in Older Adults with Mild Vascular Cognitive Impairment

2018 ◽  
Vol 2 (2) ◽  
pp. 157-169 ◽  
Author(s):  
Lisanne F. ten Brinke ◽  
Chun Liang Hsu ◽  
John R. Best ◽  
Cindy K. Barha ◽  
Teresa Liu-Ambrose
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Cortical Thickness ◽  
Aerobic Fitness ◽  
Vascular Cognitive Impairment

scholarly journals AEROBIC TRAINING, THE DEFAULT MODE NETWORK, AND COGNITION IN OLDER ADULTS WITH MILD VASCULAR COGNITIVE IMPAIRMENT

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S55-S55
Author(s):  
Rachel A Crockett ◽  
Chun Liang Hsu ◽  
Cindy Barha ◽  
Ging-Yuek Robin Hsiung ◽  
Teresa Liu-Ambrose
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Functional Connectivity ◽  
Default Mode Network ◽  
Resting State ◽  
Aerobic Training ◽  
Vascular Cognitive Impairment ◽  
Default Mode ◽  
Global Cognitive Function

Abstract Aerobic training has been shown to be effective at improving cognitive and brain outcomes in older adults with mild subcortical ischemic vascular cognitive impairment (SIVCI). However, uncertainty remains regarding the underlying neurobiological mechanisms by which exercise elicits these improvements in cognition. Increased aberrant functional connectivity of the default mode network has been highlighted as a factor contributing to cognitive decline in older adults with cognitive impairment. Greater connectivity of the DMN at rest is associated with poorer performance on attention-demanding tasks, indicative of a lack of ability to deactivate the network on task. Our previous work on a randomized controlled trial of participants with mild SIVCI, demonstrated that 6-months of thrice weekly aerobic training led to improved global cognitive function, as measured by Alzheimer’s disease Assessment Scale-Cognitive subscale (ADAS-Cog), compared with a health education program. Thus, we conducted secondary analyses to investigate whether these changes in global cognitive function were associated with changes in resting state DMN connectivity. A subsample of 21 participants underwent a resting state functional magnetic resonance imaging (fMRI) scan before and after trial completion. Change in resting state DMN connectivity was found to significantly predict change in ADAS-Cog score (β = -.442, p=.038) after controlling for age, intervention group, and baseline functional capacity (R2=.467, F(4,16)= 3.507, p=.031). These findings suggest that functional connectivity of the DMN may underlie changes in global cognitive function. Furthermore, aerobic exercise is a promising intervention by which to elicit these changes in older adults with mild SIVCI.

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