Special Issue:
Challenges and Opportunities in Aging
Hoost SS
Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Brickman AM
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Manly JJ
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Honig LS
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Gu Y
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Sanchez D
G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Reyes-Dumeyer D
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Lantigua RA
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Kang MS
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
Dage JL
Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN; Department of Neurology, Indiana University School of Medicine, Indianapolis, IN; Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine Indianapolis IN
Mayeux R
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Abstract
Background: Comorbidities may influence the levels of blood-based biomarkers for Alzheimer’s disease (AD). We investigated whether differences in risk factors or comorbid conditions might explain the discordance between clinical diagnosis and biomarker classifications in a multi-ethnic cohort of elderly individuals.
Aims: To evaluate the relationship of medical conditions and other characteristics, including body mass index (BMI), vascular risk factors, and head injury, with cognitive impairment and blood-based biomarkers of AD, phosphorylated tau (P-tau 181, P-tau 217), in a multi-ethnic cohort.
Methods: Three-hundred individuals, aged 65 and older, were selected from a prospective community-based cohort for equal representation among three racial/ethnic groups: non-Hispanic White, Hispanic/Latino and African American/Black. Participants were classified into four groups based on absence (Asym) or presence (Sym) of cognitive impairment and low (NEG) or high (POS) P-tau 217 or P-tau 181 levels, determined previously in the same cohort: (Asym/NEG, Asym/POS, Sym/NEG, Sym/POS). We examined differences in individual characteristics across the four groups. We performed post-hoc analysis examining the differences across biomarker and cognitive status.
Results: P-tau 217 or P-tau 181 positive individuals had lower BMI than P-tau negative participants, regardless of symptom status. Symptomatic and asymptomatic participants did not differ in terms of BMI. BMI was not a mediator of the effect of P-tau 217 or P-tau 181 on dementia. Frequencies of other risk factors did not differ between the four groups of individuals.
Conclusions: Participants with higher levels of P-tau 217 or P-tau 181 consistent with AD had lower BMI regardless of whether the individual was symptomatic. These findings suggest that weight loss may change with AD biomarker levels before onset of cognitive decline. They do not support BMI as a confounding variable. Further longitudinal studies could explore the relationship of risk factors with clinical diagnoses and biomarkers.
Michael Leone
Institute for Aging Research, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA
Nir Barzilai
Institute for Aging Research, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA
Abstract
The biological mechanisms of aging drive the development of chronic diseases such as cardiovascular disease, diabetes, dementia, and cancer that dominate our current medical system. Geroscience-guided approaches seek to mitigate these pathological consequences of aging by targeting the fundamental hallmarks of aging. Using modalities that modulate these aging mechanisms to reinforce longevity we can prevent the onset of these diseases as well as target many of them at once. In this way, geroscience-guided approaches hope to extend both lifespan and healthspan in the near future. This article builds upon a previous paper which proposed a standardized process for evaluating FDA-approved medications for their geroscience potential and prioritized them to reflect preclinical and clinical evidence. In this article, we provide an update of the previous list of candidate gerotherapeutics to reflect the new and rapidly evolving evidence. We include the geroscience-guided evidence for three new FDA-approved drugs which did not have strong arguments for inclusion before: bisphosphonates, GLP-1 receptor agonists, beta blockers. This updated prioritization should help guide the efforts and financial investments for translating geroscience and allow immediate progress involving such candidate gerotherapeutics, especially the top 4 drugs: SGLT2 inhibitors, metformin, bisphosphonates, and GLP-1 receptor agonists. Since all of these drugs have been approved for safety and used extensively, repurposing them as gerotherapeutics should be considered in older adults.
Abstract
Although it is known that APOE genotype is the strongest genetic risk factor for late-onset Alzheimer’s disease, development is a multifactorial process. Alcohol use is a contributor to the epidemic of Alzheimer’s disease and related dementias in the US and globally, yet mechanisms are not fully understood. Carriers of the APOE ε 4 allele show elevated risk of dementia in relation to several lifestyle factors, including alcohol use. In this review, we describe how alcohol interacts with APOE genotype and aging with potential implications for Alzheimer’s disease promotion. Age-related immune senescence and “inflammaging” (i.e., low-grade inflammation associated with aging) are increasingly recognized as contributors to age-related disease. We focus on three immune pathways that are likely contributors to Alzheimer’s disease development, centering on alcohol and APOE genotype interactions, specifically: 1) microbial translocation and immune activation, 2) the senescence associated secretory phenotype, and 3) neuroinflammation. First, microbial translocation, the unphysiological movement of gut products into systemic circulation, elicits a proinflammatory response and increases with aging, with proposed links to Alzheimer’s disease. Second, the senescence associated secretory phenotype is a set of intercellular signaling factors, e.g., proinflammatory cytokines and chemokines, growth regulators, and proteases, that drives cellular aging when senescent cells remain metabolically active. The senescence associated secretory phenotype can drive development of aging-diseases such as Alzheimer’s disease. Third, neuroinflammation occurs via numerous mechanisms such as microglial activation and is gaining recognition as an etiological factor in the development of Alzheimer’s disease. This review focuses on interactions of alcohol with APOE genotype and aging along these three pathways that may promote Alzheimer’s disease. Further research on these processes may inform development of strategies to prevent onset and progression of Alzheimer’s disease and to delay associated cognitive decline.
Abstract
The world is now well into the third decade of use of effective anti-retroviral therapy (ART) that provides sustained control of HIV-1 viremia (viral loads <200 copies of HIV RNA/microliter). With few exceptions, control of HIV in individual patients is predictable and long lasting. Only a short time ago, the prevailing opinion was that HIV infection ‘physiologically aged’ an individual by ten years or more compared to uninfected subjects and could lead to premature frailty. 1-4 Whereas these findings may have accurately characterized the untreated HIV-infected individual, they do not apply to those on ART. We discuss these concepts and show why they have not held up to scrutiny. Clinical and cellular evidence contradict these statements. Theories about aging in HIV-positive patients arose in the early 2000’s 5 about the time we began to study the course of HIV infection in our clinics, measuring frailty as well as obtaining and preserving blood samples from HIV- and healthy, age-matched control patients allowing us to study cellular aging and immunity as well as the molecular features of HIV genes in viral quasispecies suppressed by ART.
One deleterious outcome of aging may be frailty, once believed to be an ineluctable outcome of aging HIV-infected patients. Most clinicians probably would not argue with a definition of frailty such as, “you’ll know it when you see it.” However useful this definition may be in practice measurable parameters of frailty are needed to conduct a study. We chose to use a phenotypic measurement of frailty, the so-called Fried criteria 6 that are easily and rapidly obtained in the clinic at each visit. 7 The Fried method provides ordinate values for 5 functional aspects of health observed in aging individuals: shrinking weight, slowness, weakness in grip strength, low physical activity and exhaustion. The diagnosis of frailty using these criteria require that any three of such measurements be abnormal. 8 There are many “surrogate measurements of frailty” for HIV patients, the most popular being the “frailty index” wherein one adds up diseases over a lifetime. This information can be obtained from the history and records. However, directly observing our patients in the clinic and measuring for frailty gave us the clue that “frailty” was not permanent, and thus, decline was not inevitable as was held for the uninfected elderly. 9 We found that frailty in HIV patients, with few exceptions, was transient (i.e., reversible), lessened with time clearly related to increasing CD4 cell counts and suppressed viremia due to use of antiretroviral drugs. 10
Darlene E. Berryman
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA; Diabetes Institute, Ohio University, Athens, Ohio 45701, USA
Edward O. List
Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Grace Lach
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Jonathan A. Young
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Zoe A. Kington
Honors Tutorial College, Ohio University, Athens, Ohio 45701, USA
John J. Kopchick
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Abstract
A reduction in growth hormone has repeatedly been shown to improve healthspan and lifespan in mice and attenuate age-related conditions in subsets of comparable clinical populations. While aging results in progressive physiological changes in many tissues that leads to declines in biological function, this review will focus on the role of growth hormone in adipose tissue with respect to the aging process. Growth hormone dramatically and uniquely alters adipose tissue mass, composition, function and distribution, with decreases in hormone action resulting in a counterintuitive “healthy obese” state. As clinical studies are somewhat limited, much of our understanding of this hormone’s unique effect on adipose tissue and aging comes from mouse lines with specific alterations to the growth hormone axis. Thus, this review will provide an overview of the health span and lifespan consequences of growth hormone action in mouse lines and briefly describe comparable clinical conditions. The review will also summarize the general changes in adipose tissue with normal aging as well as the unique changes in this tissue in response to growth hormones.
Darlene E. Berryman
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA; Diabetes Institute, Ohio University, Athens, Ohio 45701, USA
Edward O. List
Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Grace Lach
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Jonathan A. Young
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Zoe A. Kington
Honors Tutorial College, Ohio University, Athens, Ohio 45701, USA
John J. Kopchick
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Abstract
A reduction in growth hormone has repeatedly been shown to improve healthspan and lifespan in mice and attenuate age-related conditions in subsets of comparable clinical populations. While aging results in progressive physiological changes in many tissues that leads to declines in biological function, this review will focus on the role of growth hormone in adipose tissue with respect to the aging process. Growth hormone dramatically and uniquely alters adipose tissue mass, composition, function and distribution, with decreases in hormone action resulting in a counterintuitive “healthy obese” state. As clinical studies are somewhat limited, much of our understanding of this hormone’s unique effect on adipose tissue and aging comes from mouse lines with specific alterations to the growth hormone axis. Thus, this review will provide an overview of the healthspan and lifespan consequences of growth hormone action in mouse lines and briefly describe comparable clinical conditions. The review will also summarize the general changes in adipose tissue with normal aging as well as the unique changes in this tissue in response to growth hormone.
Papitchaya Watcharanurak
Faculty of Medical Technology, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
Apiwat Mutirangura
Center of Excellence in Molecular Genetics of Cancer and Human Disease, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
Abstract
Background: Age-associated epigenetic alteration is the underlying cause of DNA damage in aging cells. Two types of youth-associated DNA-protection epigenetic marks, global methylation, and youth-associated genomic stabilization DNA gap (youth-DNA-gap) reduce when cell ages. The epigenomic mark reduction promotes DNA damage and accelerates aging hallmarks. While DNA hypomethylation destabilizes DNA by several mechanisms, the DNA sequence around the youth-DNA-gap is hypermethylated. Therefore, the genomic instability mechanisms underlying DNA hypomethylation and youth-DNA-gap reduction are linked.
Results: DNA gap prevents DNA damage by relieving the torsion forces caused by a twisted wave during DNA strand separation by transcription or replication. When the cells begin to age, hypomethylation and youth-DNA-gap reduction can occur as consequences of the efflux of intranuclear HMGB1. The methylated DNA gaps are formed by several proteins. Box A of HMGB1 possesses a molecular scissor role in producing youth-DNA-gaps. So the lack of a gap-producing role of HMGB1 results in a youth-DNA-gap reduction. The histone deacetylation role of SIRT1, an aging prevention protein, prevents DNA ends of youth-DNA-gaps from being recognized as pathologic DNA breaks. Youth-DNA-gaps are methylated and determined genome distribution by AGO4, an effector protein in RNA-directed DNA methylation. The lack of intranuclear HMGB1 promotes global hypomethylation due to two subsequent mechanisms. First is the loss of AGO4-methylating DNA. The other is the accumulation of DNA damage due to lacking HMGB1-produced DNA gap promoting DNA demethylation while undergoing DNA repair. DNA torsion due to youth-DNA-gap reduction increases DNA damage and, consequently, the DNA damage response (DDR). Persistent DDR promotes cellular senescence. Accumulating senescent cells leads to the deterioration of the structure and function of the human body. Rejuvenating DNA (RED) by adding DNA protection epigenetic marks using genomic stability molecule (GEM) such as box A of HMGB1 increases DNA durability, limits DNA damage, rejuvenates senescence cells, and improves organ structure and function deterioration due to aging.
Conclusion: Reducing youth-associated epigenetic marks is degenerative diseases’ primary molecular pathogenesis mechanism. REDGEM is a new therapeutic strategy inhibiting the upstream molecular aging process that will revolutionize the treatment of DNA damage or age-associated diseases and conditions.
Pegah Derakhshan
Graduate Program in Rehabilitation Sciences, UBC, Vancouver, BC, CA; Centre for Aging Smart Rehabilitation Research Program, GF Strong Rehabilitation, UBC, Vancouver, BC, CA; International Collaboration on Repair Discoveries (ICORD), Vancouver, BC, CA
William C. Miller
Centre for Aging Smart Rehabilitation Research Program, GF Strong Rehabilitation, UBC, Vancouver, BC, CA; International Collaboration on Repair Discoveries (ICORD), Vancouver, BC, CA; Department of Occupational Science & Therapy, UBC, Vancouver, BC, CA
Ethan Simpson
Centre for Aging Smart Rehabilitation Research Program, GF Strong Rehabilitation, UBC, Vancouver, BC, CA; International Collaboration on Repair Discoveries (ICORD), Vancouver, BC, CA; Department of Occupational Science & Therapy, UBC, Vancouver, BC, CA
Christopher B. McBride
Spinal Cord Injury British Columbia, Vancouver, BC, CA
Jaimie Borisoff
International Collaboration on Repair Discoveries (ICORD), Vancouver, BC, CA ; Department of Occupational Science & Therapy, UBC, Vancouver, BC, CA; British Columbia Institute of Technology (BCIT), Burnaby, CA
Julia Schmidt
Centre for Aging Smart Rehabilitation Research Program, GF Strong Rehabilitation, UBC, Vancouver, BC, CA; Department of Occupational Science & Therapy, UBC, Vancouver, BC, CA
W. Ben Mortenson
Centre for Aging Smart Rehabilitation Research Program, GF Strong Rehabilitation, UBC, Vancouver, BC, CA; International Collaboration on Repair Discoveries (ICORD), Vancouver, BC, CA; Department of Occupational Science & Therapy, UBC, Vancouver, BC, CA
Abstract
Introduction: During the COVID-19 pandemic, there was an urgent need for information on dealing with it among people with spinal cord injuries (SCI). Organizations provided resources, but many of them were generic. In some cases, the information was provided by dubious sources, contradictory, or not assessed for usability with individuals with SCI. This study reviewed COVID-19 web-based resources for individuals with SCI and evaluated their quality.
Methods: A scoping review for COVID-19-related web-based resources for individuals with SCI was performed by first identifying SCI-relevant organizations and, subsequently, targeted website searching using a systematic search strategy in May 2021. The included resources were categorized based on their content and format (e.g., video, infographic, text). The resources were evaluated using tools that had been previously validated.
Results: Our search identified 71 SCI organizations and 10,538 potential resources. Based on inclusion and exclusion criteria, 112 resources were included and categorized based on their content into ten main domains: prevention, caregivers, exercise, mental health, stories, telehealth, specific organs/systems, report of evidence, SCI network COVID-19 response and COVID-19 communication rights toolkit. The average score for the quality of the text, infographic, and video resources are 9.72/28 (Range:3-24), 37.75/44 (Range:35-41), and 59.14/80 (Range: 49-75), respectively.
Conclusion: Website resources mainly focused on preventing COVID-19. Only five of them addressed telehealth during COVID-19 for individuals with SCI. The results of this study will inform the development of SCI-oriented toolkits for future pandemics.
Chunhui Yang
Department of Psychiatry, OASIS International Hospital, Beijing, China; Department of Neuropathology, Rush University Medical Center, Rush Alzheimer’s Disease Center, Chicago, USA
Julie A Schneider
Department of Neuropathology, Rush University Medical Center, Rush Alzheimer’s Disease Center, Chicago, USA
Rupal Mehta
Department of Neuropathology, Rush University Medical Center, Rush Alzheimer’s Disease Center, Chicago, USA
Tong Chen
Department of Neurology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
Zhimin Wei
Department of Pathology, The Affiliated Hospital of Qingdao University, China
Sukriti Nag
Department of Neuropathology, Rush University Medical Center, Rush Alzheimer’s Disease Center, Chicago, USA
Rongwei Huang
Fanglizhihui (Hangzhou) Biotechnology Co. Ltd., China
Abstract
The present report discusses the immune and clearance system of the central nervous system (CNS) in terms of its anatomical, physiological, and biochemical properties. There is now a growing body of evidence that progressive dysfunction of the meningeal lymphatic system should be considered as a risk factor for aging-related brain disorders. In addition, the activity of meningeal lymphatics may alter the access of CSF-carried immune neuromodulators to brain parenchyma, which is also involved in the onset of aging and AD. In the CNS clearance system, impairment of the BBB and small arteries, as well as the major protein of the end feet of astrocytes, AQP4, are associated with aging or AD. The idea of maximizing brain “waste discharge” as a new preventive or therapeutic target for neurodegenerative diseases in the context of healthy aging has been accepted.
Joseph Keenan, MD
Professor Emeritus, University of Minnesota, Department of Family Medicine & Community Health; Associate Professor of Food Science & Nutrition; Director of the University Geriatric Fellowship; Founder and first president of The American Academy of Home Care Medicine.
Abstract
The aging of the global population and the associated increase in chronic disease burden requires a paradigm shift in how we care for older adults, one that could benefit from exploring a return to nicotinic acid (NA) therapy for dyslipidemia management and niacin supplementation to support healthy aging. Despite the exceptional benefits NA demonstrated in the Coronary Drug Project for improving dyslipidemia, reducing cardiovascular disease (CVD), and enhancing longevity, it has since experienced a significant decline in usage. Several factors have contributed to this decline, including poor dosing and side effect management by providers; poor outcomes of subsequent trials that combined NA with statin drugs that, in retrospect, have been attributed to poor study design; and, a faulty meta-analysis that concluded NA did not significantly reduce CVD. In addition, recent research reveals statins increase the risk of dementia in older persons, and providers are urged to look for alternative ways to manage dyslipidemia. One alternative is NA. This review explains the factors that led to the decline in NA use, provides an overview of the lipid and non-lipid effects of niacin (as NA or nicotinamide) for treating dyslipidemia and other age-related diseases, describes clinical protocols that promote efficacy and patient compliance, and identifies other factors that may contribute to a revival of niacin usage, or a “Niacin Rebirth.”
van der Aa H.P.A
van Nassau F
Rozemeijer S.C.A.
Schakel W.
van Rens G.H.M.B.
Amsterdam UMC, location Vrije Universiteit Amsterdam, Ophthalmology, De Boelelaan 1117, Amsterdam, The Netherlands
van Nispen R.M.A.
Amsterdam UMC, location Vrije Universiteit Amsterdam, Ophthalmology, De Boelelaan 1117, Amsterdam, The Netherlands / Amsterdam Public Health, Quality of Care, Mental Health, Aging and Later Life, Amsterdam, The Netherlands
Abstract
Purpose: Mental health problems are common in patients with macular oedema, who receive repeated intravitreal injections with anti-vascular endothelial growth factor. A guided internet-based self-help intervention, called E-PsEYE, was developed to reduce these problems. Patients were referred by their ophthalmologist to follow E-PsEYE individually at home, guided by a social worker from low vision services. Since e-mental health is new in this setting and professionals were collaborating in a novel way, barriers and facilitators during implementation and for future scale-up were evaluated.
Methods: Semi-structured interviews were performed with patients (n=8), ophthalmologists (n=4), heads of ophthalmology departments (n=2), doctor’s assistants (n=3), social workers (n=6) and managers from low vision services (n=2), and representatives from a health insurer (n=2). Data were analyzed using a thematic approach.
Results: Both patients and professionals were satisfied with the potential efficiency and added value of the intervention. They indicated that sufficient digital skills in patients and social workers, information technology (IT) support and adding personalized face-to-face contacts, could facilitate implementation. However, a high workload within the different settings (i.e., hospital and low vision services) and the reluctance of both patients and professionals in focusing on mental health problems could hinder implementation. Moreover, evidence on cost-effectiveness and incorporation in current guidelines were expected to be important for reimbursement and scale-up.
Conclusions: Both on the individual level and in the interaction between stakeholders and their context, different important barriers and facilitators were expressed. To facilitate the use of E-PsEYE in practice, strategies that focus on these aspects could be implemented, e.g. healthcare providers could discuss and normalize mental health complaints and their digital skills could be supported.
Sandra Magalhães
iBiMED: Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal; CICECO: Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Aveiro, Portugal
Manuel Teixeira
iBiMED: Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
Marisol Gouveia
iBiMED: Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
Fernando Ribeiro
iBiMED: Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal; ESSUA: School of Health Sciences, University of Aveiro, Aveiro, Portugal
Brian J Goodfellow
CICECO: Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Aveiro, Portugal
Alexandra Nunes
iBiMED: Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
Abstract
The loss of proteostasis is a key hallmark of aging and has been well documented using several model systems. However, in biofluids such as blood plasma, little is known about how the loss of proteostasis affects protein conformation during aging.
Our previous work has demonstrated age-related changes in protein conformation in human plasma samples using FTIR spectroscopy and conformation-specific antibodies. To prove the potential of spectroscopy to detect slight changes in protein secondary structure during aging, we have applied the same methodology to a new and independent set of 24 human plasma samples from donors with ages ranging from 40 to 75 years.
The results clearly show that from middle to old age there is a decrease in antiparallel β-sheet structures and an increase in intermolecular β-sheets, indicative of an increase in aggregation-prone proteins in human plasma over time. This confirms the potential of FTIR spectroscopy as a technique to evaluate protein conformational changes related to health and disease and as a suitable method to be used in a clinical setting to produce quick and reliable results.
