scholarly journals Absence of age-related neurodegenerative changes during SIV infection and treatment in aged macaques

Author(s):  
CA Wiley ◽  
SJ Bissel

The advent of combined antiretroviral therapy (CART) has changed HIV infection from a lethal disease to a chronic infection. CART has substantially mitigated infection-associated immunosuppression, related opportunistic infections and HIV encephalitis, nevertheless a substantial percentage of infected individuals are afflicted with a spectrum of HIV-associated neurological disorders (HAND). As approximately 45% of HIV-infected subjects in developed countries are over the age of 50, it has been hypothesized that infection may exacerbate age related neurodegenerative processes. We used the nonhuman primate SIV infection model to test whether chronic infection of aged primates, with or without CART, is associated with accelerated age-related neurodegeneration. Two dozen aged macaques (average age 18 years at entry 20 years at the end) were divided into two groups, half infected with SICmac251 and the other half not. After 10 months, half of each of these groups were either treated or not with CART and followed for an additional 6 months. We previously reported the clinical and neurobehavioural outcome. Here we compared the molecular and histologic findings in the four groups. Using a broad spectrum of histological markers, we found no evidence in the macaques of neuropathological changes associated with aging in humans. While the number of animals is small and length of infection limited, this study does not support the hypothesis that lentiviral infection or treatment accelerates age-related neurodegenerative changes in the primate brain.LEARNING OBJECTIVESThis presentation will enable the learner to:1.Explore current theories on the pathogenesis of lentiviral-related neuropathology2.Explain limitations of nonhuman primate models of age-related human brain changes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shigeru Honda ◽  
Yasuo Yanagi ◽  
Hideki Koizumi ◽  
Yirong Chen ◽  
Satoru Tanaka ◽  
...  

AbstractThe chronic eye disorder, neovascular age-related macular degeneration (nAMD), is a common cause of permanent vision impairment and blindness among the elderly in developed countries, including Japan. This study aimed to investigate the disease burden of nAMD patients under treatment, using data from the Japan National Health and Wellness surveys 2009–2014. Out of 147,272 respondents, 100 nAMD patients reported currently receiving treatment. Controls without nAMD were selected by 1:4 propensity score matching. Healthcare Resource Utilisation (HRU), Health-Related Quality of Life (HRQoL), and work productivity loss were compared between the groups. Regarding HRU, nAMD patients had significantly increased number of visits to any healthcare provider (HCP) (13.8 vs. 8.2), ophthalmologist (5.6 vs. 0.8), and other HCP (9.5 vs. 7.1) compared to controls after adjusting for confounding factors. Additionally, nAMD patients had reduced HRQoL and work productivity, i.e., reduced physical component summary (PCS) score (46.3 vs. 47.9), increased absenteeism (18.14% vs. 0.24%), presenteeism (23.89% vs. 12.44%), and total work productivity impairment (33.57% vs. 16.24%). The increased number of ophthalmologist visits were associated with decreased PCS score, increased presenteeism and total work productivity impairment. The current study highlighted substantial burden for nAMD patients, requiring further attention for future healthcare planning and treatment development.


Proceedings ◽  
2020 ◽  
Vol 70 (1) ◽  
pp. 84
Author(s):  
Rimjhim Agarwal ◽  
Hung T. Hong ◽  
Alice Hayward ◽  
Stephen Harper ◽  
Neena Mitter ◽  
...  

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries, such as Australia. Lutein and zeaxanthin are the only two carotenoids found in the macular region of the eye. Studies have shown that an intake of 10 mg and 2 mg per day of lutein and zeaxanthin, respectively, can reduce the rate of progression of AMD. The supply of these carotenoids can only be met through dietary sources or supplements, as these compounds cannot be synthesised by humans. Although lutein is relatively abundant in dietary sources, zeaxanthin has limited sources. In this study, eight orange and three red capsicum varieties were analysed for their carotenoid profiles by UHPLC-DAD-APCI-MS. It was observed that the principal carotenoid for seven of the orange varieties was zeaxanthin, and capsanthin for the three red varieties. One orange variety, which had a darker orange hue, had capsanthin and violaxanthin as its principal carotenoids instead of zeaxanthin. Zeaxanthin concentration (the principal carotenoid) in the seven orange varieties varied from 2.6 ± 0.5 mg/100 g to 25.27 ± 9.4 mg/100 FW, suggesting that as little as 7 g of the high-zeaxanthin line could meet the recommended daily dietary intake of 2 mg/person/day.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Oladele A. Oluwayiose ◽  
Haotian Wu ◽  
Hachem Saddiki ◽  
Brian W. Whitcomb ◽  
Laura B. Balzer ◽  
...  

AbstractParental age at time of offspring conception is increasing in developed countries. Advanced male age is associated with decreased reproductive success and increased risk of adverse neurodevelopmental outcomes in offspring. Mechanisms for these male age effects remain unclear, but changes in sperm DNA methylation over time is one potential explanation. We assessed genome-wide methylation of sperm DNA from 47 semen samples collected from male participants of couples seeking infertility treatment. We report that higher male age was associated with lower likelihood of fertilization and live birth, and poor embryo development (p < 0.05). Furthermore, our multivariable linear models showed male age was associated with alterations in sperm methylation at 1698 CpGs and 1146 regions (q < 0.05), which were associated with > 750 genes enriched in embryonic development, behavior and neurodevelopment among others. High dimensional mediation analyses identified four genes (DEFB126, TPI1P3, PLCH2 and DLGAP2) with age-related sperm differential methylation that accounted for 64% (95% CI 0.42–0.86%; p < 0.05) of the effect of male age on lower fertilization rate. Our findings from this modest IVF population provide evidence for sperm methylation as a mechanism of age-induced poor reproductive outcomes and identifies possible candidate genes for mediating these effects.


Nanoscale ◽  
2017 ◽  
Vol 9 (40) ◽  
pp. 15461-15469 ◽  
Author(s):  
Na-Kyung Ryoo ◽  
Jihwang Lee ◽  
Hyunjoo Lee ◽  
Hye Kyoung Hong ◽  
Hyejin Kim ◽  
...  

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries and is characterized by the development of choroidal neovascularization (CNV).


1983 ◽  
Vol 28 (5) ◽  
pp. 1207-1215 ◽  
Author(s):  
Byung C. Lee ◽  
Jose L. Pineda ◽  
Bessie E. Spiliotis ◽  
Teri J. Brown ◽  
Barry B. Bercu

Breathe ◽  
2016 ◽  
Vol 12 (1) ◽  
pp. 50-60 ◽  
Author(s):  
Alison McMillan ◽  
Mary J. Morrell

Key pointsSleep disordered breathing (SDB) is common and its prevalence increases with age. Despite this high prevalence, SDB is frequently unrecognised and undiagnosed in older people.There is accumulating evidence that SDB in older people is associated with worsening cardio- cerebrovascular, cognitive and functional outcomes.There is now good evidence to support the use of continuous positive airway pressure therapy in older patients with symptomatic SDB.Educational aimsTo highlight the prevalence and presentation of sleep disordered breathing (SDB) in older people.To inform readers about the risk factors for SDB in older people.To explore the impact of SDB in older people.To introduce current evidence based treatment options for SDB in older people.Sleep disordered breathing (SBD) increases in prevalence as we age, most likely due to physiological and physical changes that occur with ageing. Additionally, SDB is associated with comorbidity and its subsequent polypharmacy, which may increase with increasing age. Finally, the increased prevalence of SDB is intrinsically linked to the obesity epidemic. SDB is associated with serious outcomes in younger people and, likewise, older people. Thus, identification, diagnosis and treatment of SDB is important irrelevant of age. This article reviews the age-related changes contributing to SDB, the epidemiology and the risk factors for SDB in older people, the association of SDB with adverse outcomes, and diagnostic and treatment options for this population.


2020 ◽  
Vol 77 (5) ◽  
pp. 779-780 ◽  
Author(s):  
Anu Kauppinen

AbstractProlonged life expectancies contribute to the increasing prevalence of age-related macular degeneration (AMD) that is already the leading cause of severe vision loss among the elderly in developed countries. In dry AMD, the disease culminates into vast retinal atrophy, whereas the wet form is characterized by retinal edema and sudden vision loss due to neovascularization originating from the choroid beneath the Bruch’s membrane. There is no treatment for dry AMD and despite intravitreal injections of anti-vascular endothelial growth factor (VEGF) that suppress the neovessel formation, also wet AMD needs new therapies to prevent the disease progression and to serve patients lacking of positive response to current medicines. Knowledge on disease mechanisms is a prerequisite for the drug development, which is hindered by the multifactorial nature of AMD. Numerous distinguished publications have revealed AMD mechanisms at the cellular and molecular level and in this multi-author review, we take a bit broader look at the topic with some novel aspects.


2021 ◽  
Vol 2 ◽  
Author(s):  
Andrew V. Kuczmarski ◽  
Laura M. Welti ◽  
Kerrie L. Moreau ◽  
Megan M. Wenner

Aging is a primary risk factor for cardiovascular disease (CVD), which is the leading cause of death in developed countries. Globally, the population of adults over the age of 60 is expected to double by the year 2050. CVD prevalence and mortality rates differ between men and women as they age in part due to sex-specific mechanisms impacting the biological processes of aging. Measures of vascular function offer key insights into cardiovascular health. Changes in vascular function precede changes in CVD prevalence rates in men and women and with aging. A key mechanism underlying these changes in vascular function is the endothelin (ET) system. Studies have demonstrated sex and sex hormone effects on endothelin-1 (ET-1), and its receptors ETA and ETB. However, with aging there is a dysregulation of this system resulting in an imbalance between vasodilation and vasoconstriction. Thus, ET-1 may play a role in the sex differences observed with vascular aging. While most research has been conducted in pre-clinical animal models, we describe more recent translational data in humans showing that the ET system is an important regulator of vascular dysfunction with aging and acts through sex-specific ET receptor mechanisms. In this review, we present translational evidence (cell, tissue, animal, and human) that the ET system is a key mechanism regulating sex-specific changes in vascular function with aging, along with therapeutic interventions to reduce ET-mediated vascular dysfunction associated with aging. More knowledge on the factors responsible for the sex differences with vascular aging allow for optimized therapeutic strategies to attenuate CVD risk in the expanding aging population.


2020 ◽  
Author(s):  
Mélanie H. Thomas ◽  
Mona Karout ◽  
Beatriz Pardo Rodriguez ◽  
Yujuan Gui ◽  
Christian Jaeger ◽  
...  

AbstractMouse models have been instrumental in understanding genetic determinants of aging and its crucial role in neurodegenerative diseases. However, few studies have analyzed the evolution of the mouse brain over time at baseline. Furthermore, mouse brain studies are commonly conducted on the C57BL/6 strain, limiting the analysis to a specific genetic background. In Parkinson’s disease, the gradual demise of nigral dopaminergic neurons mainly contributes to the motor symptoms. Interestingly, a decline of the dopaminergic neuron function and integrity is also a characteristic of physiological aging in some species. Age-related nigro-striatal features have never been studied in mice of different genetic backgrounds. In this study, we analyze the morphological features in the striatum of three common mouse strains, C57BL/6J, A/J, and DBA/2J at 3-, 9- and 15 months of age. By measuring dopaminergic markers, we uncover age-related changes that differ between strains and evolve dynamically over time. Overall, our results highlight the importance of considering background strain and age when studying the murine nigro-striatal circuit in health and disease.HighlightsStudy of the integrity of the nigro-striatal circuit in C57BL/6J, A/J, and DBA/2J at different agesAge related evolution of essential features of nigral dopaminergic neurons differ between strainsConsider background strain and age is crutial to study the nigrostriatal circuit in health and disease


2018 ◽  
Author(s):  
Lea M. Bartsch ◽  
Vanessa M. Loaiza ◽  
Lutz Jäncke ◽  
Klaus Oberauer ◽  
Jarrod A. Lewis-Peacock

AbstractMaintenance of information in working memory (WM) is assumed to rely on refreshing and elaboration, but clear mechanistic descriptions of these cognitive processes are lacking, and it is unclear whether they are simply two labels for the same process. This fMRI study investigated the extent to which refreshing, elaboration, and repeating of items in WM are distinct neural processes with dissociable behavioral outcomes in WM and long-term memory (LTM). Multivariate pattern analyses of fMRI data revealed differentiable neural signatures for these processes, which we also replicated in an independent sample of older adults. In some cases, the degree of neural separation within an individual predicted their memory performance. Elaboration improved LTM, but not WM, and this benefit increased as its neural signature became more distinct from repetition. Refreshing had no impact on LTM, but did improve WM, although the neural discrimination of this process was not predictive of the degree of improvement. These results demonstrate that refreshing and elaboration are separate processes that differently contribute to memory performance.HighlightsRepeated reading, refreshing, and elaboration are differentiable in brain activation patterns in both young and older adults.Elaboration selectively improved long-term memory for young adults, and the size of the benefit was related to the neural separability of elaboration from other processes.Older adults implemented a sub-optimal form of elaboration, and this may be a factor contributing to age-related deficits in long-term memory.Ethics statementThe study was approved by the ethical review board of the canton of Zurich (BASEC-No. 2017-00190) and all subjects gave informed written consent in accordance with the Declaration of Helsinki.Data and code availability statementAll behavioral data and analysis scripts can be assessed on the Open Science Framework (osf.io/p2h8b/). The fMRI data that support the findings of this study are available on request from the corresponding author, LMB. The fMRI data are not publicly available due to restrictions of the Swiss Ethics Committees on research involving humans regarding data containing information that could compromise the privacy of research participants.


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