Instrumentos de avaliação multidimensional de fragilidade para uso no cuidado de idosos com doença cardiovascular / Multidimensional frailty assessment tools for use in the care of older adults with cardiovascular disease / Instrumentos de evaluación multidimensional de la fragilidad en la atención de adultos mayores con enfermedad cardiovascular

Objetivo: identificar quais os instrumentos disponíveis para avaliação multidimensional da fragilidade em idosos com doença cardiovascular, potencialmente aplicáveis durante a realização do Processo de Enfermagem. Método: revisão sistemática conduzida em oito bases de dados/portais, para identificação de estudos que apresentassem instrumentos multidimensionais de avaliação de fragilidade em idosos com doença cardiovascular e que fossem aplicáveis ao processo de enfermagem. Resultados: foram incluídos 19 instrumentos multidimensionais. O Brief Frailty Index for Coronary Artery Disease foi desenvolvido para uso no cuidado cardiovascular de idosos. O Frailty Index for Adults e o Maastricht Frailty Screening Tool for Hospitalized Patients foram desenvolvidos para uso no Processo de Enfermagem. Conclusão: apesar de apenas um instrumento ter sido desenvolvido para o idosos com doença cardiovascular e apenas dois serem aplicáveis ao processo de enfermagem, a maioria deles tem potencial de adaptação e validação para uso nesta população durante a avaliação de enfermagem.

Objective: to identify which tools are available for multidimensional frailty assessment of older adult with cardiovascular disease and which are potentially applicable during the Nursing Process. Method: a systematic review conducted in eight databases/portals to identify studies that presented multidimensional frailty assessment tools for older adult with cardiovascular disease and that were applicable to the nursing process. Results: a total of 19 multidimensional tools were included. The Brief Frailty Index for Coronary Artery Disease was developed for use in the cardiovascular care of older adult. The Frailty Index for Adults and the Maastricht Frailty Screening Tool for Hospitalized Patients were developed for use in the Nursing Process. Conclusion: although only one tool was developed for older adults with cardiovascular disease and only two are applicable to the nursing process, most of them have the potential to be adapted and validated for use in this population during nursing assessment.

Objetivo: identificar qué instrumentos están disponibles para la evaluación multidimensional de la fragilidad en personas mayores con enfermedad cardiovascular, que se puedan aplicar en el Proceso de Enfermería. Método: revisión sistemática realizada en ocho bases de datos/portales, para identificar estudios que presentaran instrumentos multidimensionales para la evaluación de la fragilidad en adultos mayores con enfermedad cardiovascular y que fueran aplicables al proceso de enfermería. Resultados: se incluyeron 19 instrumentos multidimensionales. El Brief Frailty Index for Coronary Artery Disease se desarrolló para usarlo en el cuidado cardiovascular de las personas mayores. El Frailty Index for Adults y la Maastricht Frailty Screening Tool for Hospitalized Patients se elaboraron para ser usados en el Proceso de Enfermería. Conclusión: aunque sólo se elaboró un instrumento para adultos mayores con enfermedad cardiovascular y sólo dos son aplicables al proceso de enfermería, la mayoría de ellos tienen el potencial para ser adaptados y validados para ser usados en esa población en la evaluación de enfermería.

Baby Boomer Gay Men's Experiences with Primary Healthcare.

This research explored baby boomer gay men's experiences with primary healthcare and their perspectives of future long-term care. Baby boomer gay men's perspectives about primary healthcare remain understudied in the United States. A descriptive qualitative study was conducted with 30 baby boomer men in the Southwest USA. We used semi-structured interviews to assess participants' initiation and maintenance of primary healthcare, disclosure of sexual orientation to providers, and perspectives about future healthcare needs, including long-term care. Data were analyzed with a latent thematic analysis. We found baby boomer gay men anticipate discrimination because of their sexual orientation whenever they establish healthcare with new providers. Participants identified circumstantial comfort in the new healthcare setting as a key motivator to disclose their sexual orientation. Thus, baby boomer gay men specifically sought gay or gay-friendly healthcare providers to ease the burden of managing disclosure and to permit free discussion of their sexual orientation and healthcare needs. Participants faced recurring anticipation of rejection and discrimination from healthcare providers, which extends to their perceptions of current healthcare encounters and future long-term care placement. Healthcare providers would benefit from understanding the practice implications of this dynamic. Future research on primary healthcare inclusivity is needed.

Age-related changes in cheek skin movement: A case study of Japanese women.

BACKGROUND: The majority of conventional studies on skin aging have focused on static conditions. However, in daily life, the facial skin we encounter is constantly in motion due to conversational expressions and changes in facial expressions, causing the skin to alter its position and shape, resulting in a dynamic state. Consequently, it is hypothesized that characteristics of aging not apparent in static conditions may be present in the dynamic state of the skin. Therefore, this study investigates age-related changes in dynamic skin characteristics associated with facial expression alterations. METHODS: A motion capture system measured the dynamic characteristics (delay and stretchiness of skin movement associated with expression) of the cheek skin in response to facial expressions among 86 Japanese women aged between 20 and 69 years. RESULTS: The findings revealed an increase in the delay of cheek skin response to facial expressions (r = 0.24, p < 0.05) and a decrease in the stretchiness of the lower cheek area with age (r = 0.60, p < 0.01). An increasing variance in delay and stretchiness within the same age group was also observed with aging. CONCLUSION: The findings of this study revealed that skin aging encompasses both static characteristics, such as spots, wrinkles, and sagging, traditionally studied in aging research, and dynamic aging characteristics of the skin that emerge in response to facial expression changes. These dynamic aging characteristics could pave the way for the development of new methodologies in skin aging analysis and potentially improve our understanding and treatment of aging impressions that are visually perceptible in daily life but remain unexplored.

Current evidence supporting associations of DNA methylation measurements with survivorship burdens in cancer survivors: A scoping review.

INTRODUCTION: Identifying reliable biomarkers that reflect cancer survivorship symptoms remains a challenge for researchers. DNA methylation (DNAm) measurements reflecting epigenetic changes caused by anti-cancer therapy may provide needed insights. Given lack of consensus describing utilization of DNAm data to predict survivorship issues, a review evaluating the current landscape is warranted. OBJECTIVE: Provide an overview of current studies examining associations of DNAm with survivorship burdens in cancer survivors. METHODS: A literature review was conducted including studies if they focused on cohorts of cancer survivors, utilized peripheral blood cell DNAm data, and evaluated the associations of DNAm and survivorship issues. RESULTS: A total of 22 studies were identified, with majority focused on breast (n = 7) or childhood cancer (n = 9) survivors, and half studies included less than 100 patients (n = 11). Survivorship issues evaluated included those related to neurocognition (n = 5), psychiatric health (n = 3), general wellness (n = 9), chronic conditions (n = 5), and treatment specific toxicities (n = 4). Studies evaluated epigenetic age metrics (n = 10) and DNAm levels at individual CpG sites or regions (n = 12) for their associations with survivorship issues in cancer survivors along with relevant confounding factors. Significant associations of measured DNAm in the peripheral blood samples of cancer survivors and survivorship issues were identified. DISCUSSION/CONCLUSION: Studies utilizing epigenetic age metrics and differential methylation analysis demonstrated significant associations of DNAm measurements with survivorship burdens. Associations were observed encompassing diverse survivorship outcomes and timeframes relative to anti-cancer therapy initiation. These findings underscore the potential of these measurements as useful biomarkers in survivorship care and research.

Which intervention is optimal to control blood glucose and improve physical performance in the elderly living with type 2 diabetes mellitus? A network meta-analysis.

BACKGROUND AND OBJECTIVES: This study aimed to find the optimal intervention available to both control blood glucose and improve physical function in the geriatric population with T2DM. METHODS AND STUDY DESIGN: A systemic review and network meta-analysis (NMA) was conducted to assess and rank the comparative efficacy of different interventions on glycosylated hemoglobin A1c (HbAc1), fasting blood glucose (FBG), muscle mass, grip strength, gait speed, lower body muscle strength, and dynamic balance. A total of eight databases were searched for eligible randomized controlled trials (RCTs) that the elderly aged more than 60 years or with mean age ≥ 55 years, the minimal duration of the RCT intervention was 6 weeks, and those lacking data about glycemic level and at least one indicator of physical performance were excluded. The Cochrane risk of bias tool was used to assess the bias of each study included. Bayesian NMA was performed as the main results, the Bayesian meta regression and the frequentist NMA as sensitivity analysis. RESULTS: Of the 2266 literature retrieved, 27 RCTs with a total of 2289 older adults were included. Health management provided by health workers exerts beneficial effects that is superior to other interventions at achieving glycemic control, but less marked improvement in physical performance. Exercise combined with cognitive training showed more pronounced improvement in muscle strength, gait speed, and dynamic balance, but ranked behind in decreasing the HbAc1 and FBG. CONCLUSIONS: Personalized health management combined with physical and cognitive training might be the optimal intervention to both accomplish glycemic control and improvement of physical performance. Further RCTs are needed to validate and assess the confidence of our results from this NMA.

Biogenic amines in the testis: sources, receptors and actions.

Biogenic amines are signaling molecules with multiple roles in the central nervous system and in peripheral organs, including the gonads. A series of studies indicated that these molecules, their biosynthetic enzymes and their receptors are present in the testis and that they are involved in the regulation of male reproductive physiology and/or pathology. This mini-review aims to summarize the current knowledge in this field and to pinpoint existing research gaps. We suggest that the widespread clinical use of pharmacological agonists/antagonists of these signaling molecules, calls for new investigations in this area. They are necessary to evaluate the relevance of biogenic amines for human male fertility and infertility, as well as the potential value of at least one of them as an anti-aging compound in the testis.

Omega-3 polyunsatured fatty acids and physical performance across the lifespan: a narrative review.

Background and Aims: Physical performance is a major contributor of mobility and independence during older life. Despite a progressive decline in musculoskeletal function starts from middle age, several factors acting during the life-course can negatively influence musculoskeletal functional capacities. Lifestyle interventions incorporating nutrition and physical exercise can help maximizing the muscle functional capacities in early life as well as preserving them later in life. Among various dietary compounds, omega-3 polyunsaturated fatty acids (PUFAs) are gaining growing attention for their potential effects on muscle membrane composition and muscle function. Indeed, several pathways are enhanced, such as an attenuation of pro-inflammatory oxidative stress, mitochondrial function, activation of the mammalian target of rapamycin (mTOR) signaling and reduction of insulin resistance. Methods: We performed a narrative review to explore the existing literature on the relationship between omega-3 PUFAs and physical performance across the life-course. Results: Growing evidence from randomized controlled trials (RCTs) suggests beneficial effects of omega-3 PUFAs on muscle function, including physical performance parameters in mid to later life. On the other hand, despite a direct association in early life is not available in literature, some mechanisms by which omega-3 PUFAs may contribute to improved adult physical performance could be hypothesized. Conclusion: Omega-3 PUFAs are gaining growing attention for their positive effect on muscle function parameters. The integration of physical function measures in future studies would be of great interest to explore whether omega-3 PUFAs could contribute to improved muscle function, starting from early life and extending throughout the lifespan. However, larger and high-quality RCTs are needed to fully elucidate the beneficial effects of omega-3 PUFAs supplementation on muscle mass and function.

RNA-binding proteins in bone pathophysiology.

Bone remodelling is a highly regulated process that maintains mineral homeostasis and preserves bone integrity. During this process, intricate communication among all bone cells is required. Indeed, adapt to changing functional situations in the bone, the resorption activity of osteoclasts is tightly balanced with the bone formation activity of osteoblasts. Recent studies have reported that RNA Binding Proteins (RBPs) are involved in bone cell activity regulation. RBPs are critical effectors of gene expression and essential regulators of cell fate decision, due to their ability to bind and regulate the activity of cellular RNAs. Thus, a better understanding of these regulation mechanisms at molecular and cellular levels could generate new knowledge on the pathophysiologic conditions of bone. In this Review, we provide an overview of the basic properties and functions of selected RBPs, focusing on their physiological and pathological roles in the bone.

Morphology of human sinoatrial node and its surrounding right atrial muscle in the global obesity pandemic-does fat matter?

Introduction: The sinus node (SN) is the main pacemaker site of the heart, located in the upper right atrium at the junction of the superior vena cava and right atrium. The precise morphology of the SN in the human heart remains relatively unclear especially the SN microscopical anatomy in the hearts of aged and obese individuals. In this study, the histology of the SN with surrounding right atrial (RA) muscle was analyzed from young non-obese, aged non-obese, aged obese and young obese individuals. The impacts of aging and obesity on fibrosis, apoptosis and cellular hypertrophy were investigated in the SN and RA. Moreover, the impact of obesity on P wave morphology in ECG was also analyzed to determine the speed and conduction of the impulse generated by the SN. Methods: Human SN/RA specimens were dissected from 23 post-mortem hearts (preserved in 4% formaldehyde solution), under Polish local ethical rules. The SN/RA tissue blocks were embedded in paraffin and histologically stained with Masson's Trichrome. High and low-magnification images were taken, and analysis was done for appropriate statistical tests on Prism (GraphPad, USA). 12-lead ECGs from 14 patients under Polish local ethical rules were obtained. The P wave morphologies from lead II, lead III and lead aVF were analyzed. Results: Compared to the surrounding RA, the SN in all four groups has significantly more connective tissue (P ≤ 0.05) (young non-obese individuals, aged non-obese individuals, aged obese individuals and young obese individuals) and significantly smaller nodal cells (P ≤ 0.05) (young non-obese individuals, aged non-obese individuals, aged obese individuals, young obese individuals). In aging, overall, there was a significant increase in fibrosis, apoptosis, and cellular hypertrophy in the SN (P ≤ 0.05) and RA (P ≤ 0.05). Obesity did not further exacerbate fibrosis but caused a further increase in cellular hypertrophy (SN P ≤ 0.05, RA P ≤ 0.05), especially in young obese individuals. However, there was more infiltrating fat within the SN and RA bundles in obesity. Compared to the young non-obese individuals, the young obese individuals showed decreased P wave amplitude and P wave slope in aVF lead. Discussion: Aging and obesity are two risk factors for extensive fibrosis and cellular hypertrophy in SN and RA. Obesity exacerbates the morphological alterations, especially hypertrophy of nodal and atrial myocytes. These morphological alterations might lead to functional alterations and eventually cause cardiovascular diseases, such as SN dysfunction, atrial fibrillation, bradycardia, and heart failure.

Repurposing effect of cardiovascular-metabolic drug to increase lifespan: a systematic review of animal studies and current clinical trial progress.

With the increase in life expectancy, aging has emerged as a significant health concern. Due to its various mechanisms of action, cardiometabolic drugs are often repurposed for other indications, including aging. This systematic review analyzed and highlighted the repositioning potential of cardiometabolic drugs to increase lifespan as an aging parameter in animal studies and supplemented by information from current clinical trial registries. Systematic searching in animal studies was performed based on PICO: "animal," "cardiometabolic drug," and "lifespan." All clinical trial registries were also searched from the WHO International Clinical Trial Registry Platform (ICTRP). Analysis of 49 animal trials and 10 clinical trial registries show that various cardiovascular and metabolic drugs have the potential to target lifespan. Metformin, acarbose, and aspirin are the three most studied drugs in animal trials. Aspirin and acarbose are the promising ones, whereas metformin exhibits various results. In clinical trial registries, metformin, omega-3 fatty acid, acarbose, and atorvastatin are currently cardiometabolic drugs that are repurposed to target aging. Published clinical trial results show great potential for omega-3 and metformin in healthspan. Systematic Review Registration: crd.york.ac.uk/prospero/display_record.php?RecordID=457358, identifier: CRD42023457358.

Research on the anti-aging mechanisms of Panax ginseng extract in mice: a gut microbiome and metabolomics approach.

Introduction: Aged-related brain damage and gut microbiome disruption are common. Research affirms that modulating the microbiota-gut-brain axis can help reduce age-related brain damage. Methods: Ginseng, esteemed in traditional Chinese medicine, is recognized for its anti-aging capabilities. However, previous Ginseng anti-aging studies have largely focused on diseased animal models. To this end, efforts were hereby made to explore the potential neuroprotective effects of fecal microbiota transplantation (FMT) from Ginseng-supplemented aged mice to those pre-treated with antibiotics. Results: As a result, FMT with specific modifications in natural aging mice improved animal weight gain, extended the telomere length, anti-oxidative stress in brain tissue, regulated the serum levels of cytokine, and balanced the proportion of Treg cells. Besides, FMT increased the abundance of beneficial bacteria of Lachnospiraceae, Dubosiella, Bacteroides, etc. and decreased the levels of potential pathogenic bacteria of Helicobacter and Lachnoclostridium in the fecal samples of natural aged mice. This revealed that FMT remarkably reshaped gut microbiome. Additionally, FMT-treated aged mice showed increased levels of metabolites of Ursolic acid, ß-carotene, S-Adenosylmethionine, Spermidine, Guanosine, Celecoxib, Linoleic acid, etc., which were significantly positively correlated with critical beneficial bacteria above. Additionally, these identified critical microbiota and metabolites were mainly enriched in the pathways of Amino acid metabolism, Lipid metabolism, Nucleotide metabolism, etc. Furthermore, FMT downregulated p53/p21/Rb signaling and upregulated p16/p14, ATM/synapsin I/synaptophysin/PSD95, CREB/ERK/AKT signaling in brain damage following natural aging. Discussion: Overall, the study demonstrates that reprogramming of gut microbiota by FMT impedes brain damage in the natural aging process, possibly through the regulation of microbiota-gut-brain axis.

Skin microbiome profiling reveals the crucial role of microbial metabolites in anti-photoaging.

BACKGROUND: Skin microbiota is essential for health maintenance. Photoaging is the primary environmental factor that affects skin homeostasis, but whether it influences the skin microbiota remains unclear. OBJECTIVE: The objective of this study is to investigate the relationship between photoaging and skin microbiome. METHODS: A cohort of senior bus drivers was considered as a long-term unilateral ultraviolet (UV) irradiated population. 16S rRNA amplicon sequencing was conducted to assess skin microbial composition variations on different sides of their faces. The microbiome characteristics of the photoaged population were further examined by photoaging guinea pig models, and the correlations between microbial metabolites and aging-related cytokines were analyzed by high-throughput sequencing and reverse transcription polymerase chain reaction. RESULTS: Photoaging decreased the relative abundance of microorganisms including Georgenia and Thermobifida in human skin and downregulated the generation of skin microbe-derived antioxidative metabolites such as ectoin. In animal models, Lactobacillus and Streptobacillus abundance in both the epidermis and dermis dropped after UV irradiation, resulting in low levels of skin antioxidative molecules and leading to elevated expressions of the collagen degradation factors matrix metalloproteinase (MMP)-1 and MMP-2 and inflammatory factors such as interleukin (IL)-1ß and IL-6. CONCLUSIONS: Skin microbial characteristics have an impact in photoaging and the loss of microbe-derived antioxidative metabolites impairs skin cells and accelerates the aging process. Therefore, microbiome-based therapeutics may have potential in delaying skin aging.

Cross-sectional and longitudinal associations between late-life depressive symptoms and cognitive deficits: 20-year follow-up of the Kuakini Honolulu-Asia aging study.

OBJECTIVE: To examine depressed affect, somatic complaints, and positive affect as longitudinal predictors of fluid, crystallized and global cognitive performance in the Kuakini Honolulu-Asia Aging Study (HAAS), a large prospective cohort study of Japanese-American men. METHODS: We assessed 3,088 dementia-free Kuakini-HAAS participants aged 71-93 (77.1 ± 4.2) years at baseline (1991-1993). Depressive symptoms were evaluated by the Center for Epidemiologic Studies Depression (CES-D) Scale. Baseline CES-D depression subscales (depressed and positive affects; somatic complaints) were computed. The Cognitive Abilities Screening Instrument (CASI) measured cognitive performance on a 100-point scale; fluid and crystallized cognitive abilities were derived from CASI factor analysis. Cognition was also evaluated at 4 follow-up examinations over a 20-year period. Multiple regression assessed baseline CES-D subscales as predictors of cognitive change. The baseline covariates analyzed were CASI, age, education, prevalent stroke, APOE ε4 presence, and the longevity-associated FOXO3 genotype. RESULTS: Cross-sectionally, baseline CES-D subscales were related to cognitive measures; e.g., higher depressed affect was associated with lower crystallized ability (ß = -0.058, p ≤ 0.01), and somatic complaints were linked to poorer fluid ability (ß = -0.045, p ≤ 0.05) and to worse global cognitive function as measured by total CASI score (ß = -0.038, p ≤ 0.05). However, depression subscales did not significantly or consistently predict fluid ability, crystallized ability, or global cognitive performance over time. CONCLUSION: Psychological and physical well-being were associated with contemporaneous but not subsequent cognitive functioning. Assessment of depressive symptoms may identify individuals who are likely to benefit from interventions to improve mood and somatic health and thereby maintain or enhance cognition.

Lifespan differences in hippocampal subregion connectivity patterns during movie watching.

Age-related episodic memory decline is attributed to functional alternations in the hippocampus. Less clear is how aging affects the functional connections of the hippocampus to the rest of the brain during episodic memory processing. We examined fMRI data from the CamCAN dataset, in which a large cohort of participants watched a movie (N = 643; 18-88 years), a proxy for naturalistic episodic memory encoding. We examined connectivity profiles across the lifespan both within the hippocampus (anterior, posterior), and between the hippocampal subregions and cortical networks. Aging was associated with reductions in contralateral (left, right) but not ipsilateral (anterior, posterior) hippocampal subregion connectivity. Aging was primarily associated with increased coupling between the anterior hippocampus and regions affiliated with Control, Dorsal Attention and Default Mode networks, yet decreased coupling between the posterior hippocampus and a selection of these regions. Differences in age-related hippocampal-cortical, but not within-hippocampus circuitry selectively predicted worse memory performance. Our findings comprehensively characterize hippocampal functional topography in relation to cognition in older age, suggesting that shifts in cortico-hippocampal connectivity may be sensitive markers of age-related episodic memory decline.

Laboratory study on the characteristics of fresh and aged PM1 emitted from typical forest vegetation combustion in Southwest China.

The frequency and intensity of forest fires are amplified by climate change. Substantial quantities of PM1 emitted from forest fires can undergo gradual atmospheric dispersion and long-range transport, thus impacting air quality far from the source. However, the chemical composition and physical properties of PM emitted from forest fires and its changes during atmospheric transport remain uncertain. In this study, the evolution of organic carbon (OC), elemental carbon (EC), water-soluble ions, and water-soluble metals in the particulate phase of smoke emitted from the typical forest vegetation combustion in Southwest China before and after photo-oxidation was investigated in the laboratory. Two aging periods of 5 and 9 days were selected. The OC and TC mass concentrations tended to decrease after 9-days aged compared to fresh emissions. OP, OC2, and OC3 in PM1 are expected to be potential indicators of fresh smoke, while OC3 and OC4 may serve as suitable markers for identifying aged carbon sources from the typical forest vegetation combustion in Southwest China. K+ exhibited the highest abundant water-soluble ion in fresh PM1, whereas NO3- became the most abundant water-soluble ion in aged PM1. NH4NO3 emerged as the primary secondary inorganic aerosol emitted from typical forest vegetation combustion in Southwest China. Notably, a 5-day aging period proved insufficient for the complete formation of the secondary inorganic aerosols NH4NO3 and (NH4)2SO4. After aging, the mass concentration of the water-soluble metal Ni in PM1 from typical forest vegetation combustion in Southwest China decreased, while the mean mass concentrations of all other water-soluble metals increased in varying degrees. These findings provide valuable data support and theoretical guidance for studying the atmospheric evolution of forest fire aerosols, as well as contribute to policy formulation and management of atmospheric environment safety and human health.

Effects of age on oxidative stress and locomotion in the pollinator, Megachile rotundata.

Despite numerous aging studies, the relationship between oxidative stress, aging, and decline in functions such as locomotion is still debated. Insects offer a promising model for analyzing the relationship between oxidative stress and aging, because they exhibit vast differences in lifespan that may be affected by the environment, social factors, levels of activity, and aging interventions. In this study, we explore the effects of aging on oxidative stress and locomotion using the pollinator, Megachile rotundata, a species that is very mobile and active in the adult stage. Across the adult lifespan of M. rotundata, we assessed changes in walking, flight, oxidative damage, and antioxidant defenses. Our results suggest that M. rotundata experience age-related declines in flight, but not walking. Additionally, we found that oxidative damage and antioxidant capacity initially increase with age and physical activity, but then levels are maintained. Overall, these data show that M. rotundata, like some other organisms, may not perfectly follow the free radical theory of aging.

Proteomic analysis of lung responses to SARS-CoV-2 infection in aged non-human primates: clinical and research relevance.

With devastating health and socioeconomic impact worldwide, much work is left to understand the Coronavirus Disease 2019 (COVID-19), with emphasis in the severely affected elderly population. Here, we present a proteomics study of lung tissue obtained from aged vs. young rhesus macaques (Macaca mulatta) and olive baboons (Papio Anubis) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using age as a variable, we identified common proteomic profiles in the lungs of aged infected non-human primates (NHPs), including key regulators of immune function, as well as cell and tissue remodeling, and discuss the potential clinical relevance of such parameters. Further, we identified key differences in proteomic profiles between both NHP species, and compared those to what is known about SARS-CoV-2 in humans. Finally, we explored the translatability of these animal models in the context of aging and the human presentation of the COVID-19.

Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression.

BACKGROUND: Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual "omics" signature that distinguishes subjects with varying cognitive profiles. RESULTS: We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging. CONCLUSIONS: These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.

Loneliness and global cognitive functioning in racially and ethnically diverse US midlife and older adults.

Introduction: Few studies have examined the association of loneliness and cognitive functioning in the US. We used two common measures of loneliness and examined their association in a large sample of US Black, Latino, and White adults (ages ≥ 50). Methods: We analyzed Wave 3 of the National Social Life, Health, and Aging Project (N = 2,757). We examined loneliness using one item from the CES-D and the Felt Loneliness Measure (NFLM); cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA) tool, where higher scores indicated better functioning. We used weighted ordinary least squares regressions to examine the effects of loneliness (CES-D loneliness and NFLM in separate models) on MoCA scores. In exploratory analyses, we examined if these relationships varied by race and ethnicity. We adjusted all models for sociodemographic and other salient factors (e.g., chronic disease, depressive symptoms, living alone). Results: Mean age was 63.49 years, 52% were female, and 9% were Black and 6% Latino persons. Approximately 54% endorsed feeling lonely on at least one measure; 31% (CES-D) and 46% (NFLM). The relationship between loneliness measures was positive and significant, X 2 (1, N = 2,757) = 435.493 p < 0.001. However, only 40% of lonely individuals were identified as lonely on both assessments. CES-D loneliness was inversely (߈ = -0.274, p = 0.032) associated with MoCA scores and this association did not vary by race and ethnicity. Greater NFLM loneliness was positively associated (߈ = 0.445, p < 0.001) with higher MoCA scores for Latino participants only. Discussion: Loneliness appears to be an important predictor of cognitive functioning. However, the association of loneliness and cognitive functioning varied when using the CES-D loneliness item or the NFLM. Future work is needed to understand how loneliness and its clinically relevant dimensions (social, emotional, existential, chronicity) relate to global and individual cognitive domains. Research is needed with racially and ethnically diverse midlife and older adults, particularly to understand our counterintuitive finding for Latino participants. Finally, findings also support the need for research on interventions to prevent cognitive decline targeting loneliness.

The role of dynapenia and obesity on cognitive function in older adults.

BACKGROUND & AIMS: Dynapenia and obesity have been independently associated with cognitive decline in older adults, but their co-occurring effects has not been well-studied. The study objective is to examine the relationship between dynapenic-obesity and cognitive impairment in older adults 75 years and older with normal or high cognitive function at baseline over 12 years of follow-up. We hypothesize that those with dynapenic obesity will have greater odds of cognitive function impairment than those with dynapenia only, obesity only, or no dynapenia no obesity (reference group). METHODS: A total of 761 participants with a mean age of 81.5 and Mini-Mental State Examination (MMSE) > 21 at baseline were divided into four groups: no dynapenia no obesity (n = 316), obesity only (n = 142), dynapenia only (n = 217), and dynapenic obesity (n = 86). Measures included socio-demographics, medical conditions, body mass index, depressive symptoms, handgrip strength, and limitations in activities of daily living. We performed a mixed models estimate for cognitive decline for these groups over a 12-year period. Handgrip strength (HGS) was measured with a handgrip dynamometer and cognitive function was assessed with MMSE. RESULTS: Participants in the dynapenia-obesity group experienced a greater (ß = - 1.29, Standard Error = 0.60, p-value = 0.0316) cognitive decline over time compared to those in the no dynapenia and no obesity group, after controlling for all covariates. CONCLUSION: Older adults with dynapenic-obesity were at high risk of cognitive decline over time. These findings highlight the need for interventions that target both conditions in this population to help maintain cognitive health. Community-based strength training programs and educational initiatives on nutrition and diet can help older adults reduce their risk of age-related cognitive decline.