The number of old people is rising worldwide, and advancing age is a major risk factor for atherosclerotic cardiovascular disease. However, the mechanisms underlying this phenomenon remain unclear. ...In this Review, we discuss vascular intrinsic and extrinsic mechanisms of how ageing influences the pathology of atherosclerosis. First, we focus on factors that are extrinsic to the vasculature. We discuss how ageing affects the development of myeloid cells leading to the expansion of certain myeloid cell clones and induces changes in myeloid cell functions that promote atherosclerosis via inflammation, including a potential role for IL-6. Next, we describe vascular intrinsic factors by which ageing promotes atherogenesis - in particular, the effects on mitochondrial function. Studies in mice and humans have shown that ageing leads to a decline in vascular mitochondrial function and impaired mitophagy. In mice, ageing is associated with an elevation in the levels of the inflammatory cytokine IL-6 in the aorta, which participates in a positive feedback loop with the impaired vascular mitochondrial function to accelerate atherogenesis. We speculate that vascular and myeloid cell ageing synergize, via IL-6 signalling, to accelerate atherosclerosis. Finally, we propose future avenues of clinical investigation and potential therapeutic approaches to reduce the burden of atherosclerosis in old people.
SIRT6, a member of the Sirtuin family of NAD+ -dependent enzymes, has established roles in chromatin signaling and genome maintenance. Through these functions, SIRT6 protects against aging-associated ...pathologies including metabolic disease and cancer, and can promote longevity in mice. Research from the past few years revealed that SIRT6 is a complex enzyme with multiple substrates and catalytic activities, and uncovered novel SIRT6 functions in the maintenance of organismal health span. Here, we review these new discoveries and models of SIRT6 biology in four areas: heterochromatin stabilization and silencing; stem cell biology; cancer initiation and progression; and regulation of metabolic homeostasis. We discuss the possible implications of these findings for therapeutic interventions in aging and aging-related disease processes.
Telomeres shorten with age, the major risk factor for atherosclerotic cardiovascular disease (aCVD). The observation of shorter telomeres in aCVD patients thus suggested that critical telomere ...shortening may contribute to premature biological aging and aCVD. Therefore, telomere length often is suggested as a causal aCVD risk factor, a proposal supported by recent Mendelian randomization studies; however, epidemiological research has shown disappointingly low effect sizes. It therefore remains uncertain whether telomere shortening is a cause of aCVD or merely a consequence. The authors argue that elucidating the mechanistic foundation of these findings is essential for any possible translation of telomere biology to the clinic. Here, they critically evaluate evidence for causality in animal models and human studies, and review popular hypotheses and discuss their clinical implications. The authors identify 4 key questions that any successful mechanistic theory should address, and they discuss how atherosclerosis-associated local telomere attrition may provide the answers.
Continued thinning of the atmospheric ozone, which protects the earth from damaging ultraviolet radiation (UVR), will result in elevated levels of UVR reaching the earth's surface, leading to a ...drastic increase in the incidence of skin cancer. In addition to promoting carcinogenesis in skin cells, UVR is a potent extrinsic driver of age-related changes in the skin known as "photoaging." We are in the preliminary stages of understanding of the role of intrinsic aging in melanoma, and the tumor-permissive effects of photoaging on the skin microenvironment remain largely unexplored. In this Review, we provide an overview of the impact of UVR on the skin microenvironment, addressing changes that converge or diverge with those observed in intrinsic aging. Intrinsic and extrinsic aging promote phenotypic changes to skin cell populations that alter fundamental processes such as melanogenesis, extracellular matrix deposition, inflammation, and immune response. Given the relevance of these processes in cancer, we discuss how photoaging might render the skin microenvironment permissive to melanoma progression.
According to the U.S. Census, about 5.3 million older adults in the U.S. are food insecure despite the availability of multiple federally supported supplemental food programs. The reality is that ...this number likely underestimates the number of food-insecure older adults due to inadequate measurement methods. Food insecurity for older adults is a highly complex issue that goes beyond the financial resource constraints captured in the census to include factors at all levels of the Social-Ecological Model. COVID-19 made the problem even worse due to increased demand and reduced accessibility for older adults. Public/non-profit partnerships are a proven way to address this kind of complex social issue. However, there are no published studies that systematically investigated the success of this type of coalition approach in addressing older adult food insecurity. The Kūpuna Food Security Coalition (Coalition) is a community partnership formed in 2020 to address the complex issue of food insecurity among older adults in Honolulu County. This dissertation evaluated the Coalition's approach to addressing food insecurity for older adults and assessed whether their work could be replicated in other communities and whether the approach was scalable to meet demand across broad, diverse geographies. Study 1 evaluated the operating model of the Coalition, which was based on Collective Impact framework. Looking at the successes and lesson learned in the Coalition's strategy and structure, the study found that their approach worked well in addressing food insecurity among older adults in the short term and that this framework could be replicated by other public/non-profit partnerships. Study 2 developed a model, called the Older Adult Food Insecurity Index, to predict the number of food-insecure older adults at a local and national level, addressing a significant gap in available tools. Multiple factors associated with food insecurity for older adults across all levels of the Social-Ecological Model were identified, weighted by relative impact, and combined with publicly available data at a local level to create the predictive model. Using this model to predict the number of older adults in Honolulu County, which was the geographic focus of the Coalition, resulted in the likely number of food insecure older adults being 2.5 times higher than identified in the most recent census. Study 3 leveraged an adequacy performance evaluation approach to assess the scalability of the Coalition's approach, incorporating both cross-sectional and longitudinal assessments relative to the number of food insecure older adults identified in Study 2. This study found that there were no barriers to the scalability of the Coalition's approach to address food insecurity for older adults across geographies, demographics, or changes in market demand. This multi-faceted assessment of the Coalition’s approach, while identifying several opportunities, confirmed that the model was replicable and scalable for other communities and coalitions that want to address the issue of food insecurity for older adults.
While aging is typically associated with cognitive decline, some individuals are able to diverge from the characteristic downward slope and maintain very high levels of cognitive performance. By ...examining morphological characteristics of the brain using structural neuroimaging, several studies have attempted to understand these trajectories and elucidate what neurobiological factors contribute to preserved cognition throughout advanced aging. Using data from the National Alzheimer’s Coordinating Center (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI), I examined individuals aged 60 and above who demonstrated a combined performance at or above the top 50th percentile in memory and executive function, deemed as Top Cognitive Performers (TCP). In this thesis, we aimed to understand how well structural (cortical thickness, cortical volume, and white matter hyperintensity volume) and pathological (amyloid and tau burden) characteristics can be used to model TCP. As these relationships are sparsely studied in the oldest segment of our population, those 90 and above, we also utilized existing structural magnetic resonance imaging (MRI) and neuropsychological assessment data collected by The 90+ Study. Results showed that regional network-style cortical thickness both outperformed localist cingulate models and was sufficient in predicting TCP. Additionally, we were able to show that while both cortical thickness and volume models preformed similarly, cortical thickness did slightly better at predicting TCP. Though we were able to see group differences in white matter intensities in some age groups, this measure did not independently perform as well as cortical thickness. Lastly, unlike differences seen in structural correlates, TCP individuals did not exhibit group differences in PET measures of amyloid or tau. Taken together, this shows that neuroimaging biomarkers are useful in the identification of successfully aging cohorts, particularly when examining structural correlates of aging. These relationships were seen in younger and older datasets, further suggesting that MRI biomarkers are useful across the full adult lifespan.
Deterioration of the innate immune system is generally accepted as a hallmark of aging. As a consequence of immune dysregulation, the host is not able to reliably fight infection or retain a ...symbiotic relationship with gut microbes. Individuals diagnosed with immune-related pathologies demonstrate gut microbial imbalances, or dysbiosis, as well as a decline in immune cell function. Additionally, aging significantly contributes to immune cell decline. Studies in adult Drosophila melanogaster have reported age-related dysbiosis as a primary driver of immune dysfunction. The objective of this thesis is to better understand how specific physiological changes, namely microbial imbalance, and immune dysfunction, along the aging intestine affect gut and host health. Here, my data demonstrates that the consequences of chronic immune activation, in particular microbial imbalance and changes in immune cell number and function, are closely associated with immune-induced intestinal permeability. This adds weight to recently published work across multiple model organisms that highlights the key role of intestinal barrier loss as a driver of age-related decline. Detailed insight into the immune factors that drive intestinal barrier loss and how this drives age-associated decline in immune function, for example, changes in macrophages, could lead to the development of immune-targeted antiaging therapies.
O envelhecimento faz parte das etapas do desenvolvimento humano, é um fator comum a todos. Com o crescimento significativo da população idosa, surge então, uma nova demanda científica, na tentativa ...de responder às necessidades deste público e garantir que o processo do envelhecer decorra nas mais favoráveis condições. Assim, a pessoa em processo de envelhecimento vai gradativamente perdendo sua autonomia, passando a necessitar de mais assistência ou até mesmo de um cuidador para auxiliar na continuidade de suas tarefas diárias. Neste sentido, as evidências apontam que quanto maior a dependência, maiores serão as exigências de atenção e cuidados. Deste modo, o cuidador informal tornou-se fundamental para a manutenção da qualidade de vida da pessoa idosa. No entanto, as tarefas relacionadas ao cuidar de um idoso pode acometer sobrecargas físicas e/ou emocionais para o cuidador. Logo, a falta de manejos ou estratégias de enfrentamento adequados para lidar com as diversas situações estressoras relacionadas e execução das tarefas do cuidar, podem gerar no cuidador o aumento da sobrecarga e consequentemente provocar o adoecimento, tanto físico quanto psicológico. Por conseguinte, para a regulação do organismo frente tal situação, é necessário desenvolver estratégias de enfrentamento e manejo das situações de sobrecarga, para superar os desafios do cuidar diário e assim, otimizar a saúde mental e física. Neste estudo, quantitativo e transversal, participaram 42 cuidadores informais de pessoas idosas, a maioria do sexo feminino (M idade = 40.31). Relativamente aos níveis da sobrecarga dos cuidadores informais demonstrados nos resultados da Escala de Zarit, observa-se que 50.0% dos cuidadores informais apresentaram níveis leves de sobrecarga, 40.0% apresentaram níveis moderado de sobrecarga e 9.5% apresentaram níveis graves de sobrecarga. Quanto aos níveis de autonomia da pessoa idosa 76.2% apresentaram níveis de dependência leve, 16.7% apresentam níveis de dependência moderada, 2.4% apresentaram dependência grave e 4.8% níveis de dependência severa. Referente a análise das estratégias de coping, o estudo apontou que existe somente uma associação positiva fraca entre a autonomia e a estratégia de coping fuga-esquiva e não apresentou uma correlação significativa entre os níveis de autonomia e os níveis de sobrecarga.
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