Intervenciones para adultos con dependencia funcional y sus cuidadores durante la pandemia de COVID-19 / Interventions for functionally dependent adults and their caregivers during the COVID-19 pandemic

La pandemia de COVID-19 ha afectado a la población, perjudicando especialmente a los miembros de aquellos grupos sociales en situación de mayor vulnerabilidad. Estas poblaciones específicas, como aquellas con alguna dependencia funcional, podrían verse más afectadas por los efectos de la pandemia del COVID-19. Por lo tanto, el objetivo de este artículo fue describir las intervenciones para preservar la salud general, mantener la función y la independencia y prevenir la infección por COVID-19 para los adultos con dependencia funcional (ADF). Se realizó una búsqueda sistemática en bases de datos. Se revisaron los títulos y los resúmenes de cada publicación para determinar su relevancia. Dos revisores independientes accedieron a los artículos de texto completo para determinar su elegibilidad después de la selección inicial. Las búsquedas se realizaron en septiembre de 2021 y se actualizaron en enero y julio de 2022. La información encontrada se clasificó en 3 categorías: 1) ADF durante la pandemia de COVID-19; 2) ADF durante la pandemia de COVID-19 según una condición específica (condiciones neurológicas, discapacidades/deficiencias sensoriales y deterioro cognitivo), y 3) Adultos mayores con dependencia funcional. Los adultos con dependencia enfrentaron dificultades y barreras durante la pandemia por COVID-19. Las autoridades de cada país deben garantizar que los ADF tengan acceso a los servicios de rehabilitación en tiempos de crisis sanitaria. Además, es necesario aumentar la capacidad de los servicios de rehabilitación en tiempos de crisis como pandemias. De igual manera, se sugiere el fortalecimiento de estrategias como la telerehabilitación para evitar el deterioro o agravamiento de la funcionalidad de las personas dependientes. (AU)

The COVID-19 pandemic has affected the world population, especially people from social groups in a situation of greater vulnerability among people with some functional dependency. Therefore, the aim of this review was to describe interventions during the pandemic to preserve general health, maintain function and independence, and prevent COVID-19 infection for functionally dependent adults (FDA). A systematic search in databases was carried out. Titles and abstracts of each publication were reviewed for relevance. Full-text articles were accessed by two independent reviewers. The information found was classified into three categories: 1) FDA during the COVID-19 pandemic, 2) FDA during the COVID-19 pandemic according to a specific condition (neurological conditions, sensory disabilities/impairments, and cognitive impairment), and 3) Older adults with functional dependence. The FDAs have faced difficulties and barriers during the COVID-19 pandemic. Strengthening strategies such as telerehabilitation is suggested to avoid deterioration or aggravation of the functionality of dependent people. (AU)

Demandas clínicas e intervenções de enfermagem em consultas gerontológicas: Revisão integrativa / Demandas Clínicas e intervenciones de Enfermería en consultas gerontológicas: Una revisión integrativa / Clinical demands and nursing interventions in gerontological consultations: An integrative review

Resumen Introdução: A criação de guias que unificam as demandas clínicas prevalentes em consultas de enfermagem gerontológica e, das suas respectivas intervenções, se faz presente, devido a heterogeneidade das patologias emergentes no processo de envelhecimento, que irão precisar de cuidados. Objetivo: Identificar as demandas clínicas em consultas de enfermagem gerontológica e, as intervenções implementadas pelos(as) enfermeiros(as). Método: Revisão integrativa de pesquisas originais, publicadas entre 2018 e 2022, em inglês, espanhol e português, disponíveis nas bases de dados Scopus, MEDLINE/PubMed, BIREME/LILACS/BDENF/IBECS/BVS, SciELO e Google Scholar, pelos descritores DeCS/MESH: "Idoso"; "Enfermagem no Consultório"; "Enfermagem Geriátrica" e "Geriatria". O Rating System for the Hierarchy of Evidence for Intervention foi usado para determinar o nível de evidência da amostra final. Foram excluídos editoriais, estudos de revisão e artigos duplicados. A análise dos dados se deu pela leitura analítica e interpretativa, guiadas por um checklist. Resultados: Oito artigos foram selecionados e trouxeram demandas clínica tais como: o déficit no autocuidado para banho; autonegligência; fadiga; risco de integridade da pele prejudicada; desesperança; tristeza e depressão. As intervenções se relacionaram ao incentivo ao autocuidado; otimização dos medicamentos; estímulo a atividade física; cuidados com a pele; aconselhamento; musicoterapia e reabilitação psicossocial. Conclusão: Demandas clínicas atendidas nas consultas de enfermagem gerontológica possuem grande variação, com prevalência no domínio atividade/repouso, tais como intervenções voltadas para o tratamento e prevenção de doenças e ações visando a promoção da saúde, tendo o domínio comportamental mais expressivo.

Resumen Introducción: La creación de guías que unifiquen las demandas clínicas prevalentes en las consultas de enfermería gerontológica y sus respectivas intervenciones es necesaria, debido a la heterogeneidad de patologías emergentes en el proceso de envejecimiento que requerirán cuidados. Objetivo: Identificar las demandas clínicas en las consultas de enfermería gerontológica y las intervenciones implementadas por el personal de enfermería. Método: Revisión integrativa de investigaciones originales, publicadas entre 2018 y 2022, en inglés, español y portugués, en las bases de datos Scopus, MEDLINE/PubMed, BIREME/LILACS/BDENF/IBECS/BVS, SciELO y Google Scholar. Se utilizaron los descriptores DeCS/MESH: "Idoso"; "Enfermagem no Consultório"; "Enfermagem Geriátrica" e "Geriatria". Para determinar el nivel de evidencia de la muestra final, se usó el Rating System for the Hierarchy of Evidence for Intervention. Además, se excluyeron los editoriales, los estudios de revisión y los artículos duplicados. Los datos se analizaron mediante lectura analítica e interpretativa, guiada por una lista de verificación. Resultados: Se seleccionaron ocho artículos que aportaron demandas clínicas como déficit en el autocuidado para el baño, autodescuido, fatiga, riesgo integridad de la piel perjudicada; desesperanza, tristeza y depresión. Las intervenciones estaban orientadas al fomento del autocuidado, la optimización de la medicación, el fomento de la actividad física, el cuidado de la piel, el asesoramiento, la musicoterapia y la rehabilitación psicosocial. Conclusión: Las demandas clínicas atendidas en las consultas de enfermería gerontológica son muy variadas, con predominio en el dominio actividad/reposo, como intervenciones dirigidas al tratamiento y prevención de enfermedades y acciones dirigidas a la promoción de la salud, siendo más expresivo el dominio conductual.

Abstract Introduction: The creation of guidelines that unify the prevalent clinical demands from gerontological nursing consultations and their corresponding interventions are necessary due to the heterogeneity of emerging pathologies in the aging process that will require nursing care. Objective: To identify clinical demands in gerontological nursing consultations and the interventions implemented by nurses. Method: An integrative review of original research published from 2018 and 2022, in English, Spanish, and Portuguese, in Scopus, MEDLINE/PubMed, BIREME/lilacs/BDENF/IBECS/VHL, SciELO, and Google Scholar databases, using the DeCS/MESH descriptors: "Elderly", "Nursing in the Office", "Geriatric Nursing", and "Geriatrics". The Rating System for the Hierarchy of Evidence for Intervention was used to determine the level of evidence of the final sample. Editorials, review studies, and duplicate articles were excluded. The data were analyzed by analytical and interpretative reading, guided by a checklist. Results: Eight articles were selected that showed clinical demands such as deficits in self-care for bathing, self-negligence, fatigue, risk of damaged skin integrity, hopelessness, sadness, and depression. Interventions were related to encouraging self-care, medication optimization, encouragement of exercise, skin care, counseling, music therapy, and psychosocial rehabilitation. Conclusion: There are many different clinical demands in gerontological nursing consultations, especially associated with the domain of activity/rest. These include interventions to treat and prevent diseases, and actions aimed at health promotion, in most cases associated with the behavioral domain.

Visualizing subcellular changes in the NAD(H) pool size versus redox state using fluorescence lifetime imaging microscopy of NADH.

NADH autofluorescence imaging is a promising approach for visualizing energy metabolism at the single-cell level. However, it is sensitive to the redox ratio and the total NAD(H) amount, which can change independently from each other, for example with aging. Here, we evaluate the potential of fluorescence lifetime imaging microscopy (FLIM) of NADH to differentiate between these modalities.We perform targeted modifications of the NAD(H) pool size and ratio in cells and mice and assess the impact on NADH FLIM. We show that NADH FLIM is sensitive to NAD(H) pool size, mimicking the effect of redox alterations. However, individual components of the fluorescence lifetime are differently impacted by redox versus pool size changes, allowing us to distinguish both modalities using only FLIM. Our results emphasize NADH FLIM's potential for evaluating cellular metabolism and relative NAD(H) levels with high spatial resolution, providing a crucial tool for our understanding of aging and metabolism.

Understanding the implementation and sustainability needs of evidence-based programs for racial and ethnic minoritized older adults in under-resourced communities with limited aging services.

BACKGROUND: Evidence-based programs (EBPs) for older adults effectively improve health outcomes. However, there is a limited understanding of the unique needs of service providers as they consider adopting, implementing, and maintaining programs for older minority adults in low-income communities with limited aging services. METHODS: We conducted semi-structured interviews with key informants of community-based organizations (CBOs) to understand implementation and sustainability needs of CBOs within four racial and ethnically diverse Los Angeles County geographic areas. We performed thematic analysis of interview transcripts. RESULTS: Interviews were conducted with representatives from 25 senior-serving agencies providing aging-related EBPs. CBO representatives reported implementing EBPs in 8 domains: Falls Prevention (68%), Mental Health (64%), Caregiver Health (48%), Chronic Disease Management (48%), Diabetes Management (36%), Arthritis Management (28%), Physical Activity (24%), and Multiple Conditions Management (8%). Themes are presented using the six domains of the Bass and Judge framework for factors impacting successful and sustained EBP implementation. CBOs in low-income and diverse communities described unique challenges with tailoring interventions based on local community context (literacy, language), cultural context, and locally available resources (technology, safe community spaces, transportation) and faced resource-intensive administrative burdens through staff turnover, data collection, sustainable funding, and networking. CONCLUSIONS: Serving racial and ethnic communities has unique challenges that require tailored approaches and additional resources to ensure equitable access to EBPs for all communities. We describe suggestions for enhancing the effective adoption of EBPs among service agencies in under-resourced and diverse aging communities serving populations with aging-related health disparities.

Loneliness Predicts Progression of Frailty in Married and Widowed, but Not Unmarried Community Dwelling Older Adults.

BACKGROUND: Loneliness is highly prevalent among older adults and is associated with frailty. Most studies consider loneliness in isolation without consideration for structural and functional measures of social relationships - and longitudinal studies are scarce. OBJECTIVES: This study examined longitudinal associations between loneliness and frailty and analyzed how structural and functional social measures influence these associations. DESIGN: Linear mixed effects models examined longitudinal associations between loneliness and frailty assessed with the frailty index (scale 0-100). Models were adjusted for baseline age, gender, education, depressive symptoms, global cognition, and structural (e.g., social network, marital status), and functional social measures (e.g., social, cognitive, and physical activity, and social support). PARTICIPANTS: Loneliness and frailty data from 1,931 older adults without dementia at baseline from the Rush Memory and Aging Project were examined (mean age 79.6 ± 7.7 years, 74.9% female). MEASUREMENTS: Baseline loneliness assessed by the de Jong Gierveld Loneliness Scale was the predictor of interest. RESULTS: Frailty increased significantly over a mean follow-up period of 4.6 years. Effects of loneliness on frailty were modified by marital status. Loneliness predicted an additional accumulation of 0.37 and 0.34 deficits on the frailty index per year in married and widowed individuals respectively, compared to those who were not lonely (married: p=0.009, CI 0.09, 0.64; widowed: p=0.005, CI 0.1, 0.58). Loneliness did not predict frailty progression in unmarried individuals. CONCLUSIONS: Loneliness predicts frailty progression, highlighting the importance of social determinants on physical health in aging.

Wearable Technologies for Healthy Ageing: Prospects, Challenges, and Ethical Considerations.

Digital technologies hold promise to modernize healthcare. Such opportunity should be leveraged also to address the needs of rapidly ageing populations. Against this backdrop, this paper examines the use of wearable devices for promoting healthy ageing. Previous work has assessed the prospects of digital technologies for health promotion and disease prevention in older adults. However, to our knowledge, ours is one of the first attempts to specifically address the use of wearables for healthy ageing, and to offer ethical insights for assessing the prospects of leveraging wearable devices in this context. We provide an analysis of the considerable opportunities associated with the use of wearables for healthy ageing, with a focus on the five domains of intrinsic capacity: locomotion, sensory functions, psychological aspects, cognition, and vitality. We then highlight current limitations and ethical challenges of such approach to healthy ageing, including issues related to access, inclusion, privacy, surveillance, autonomy, and regulation. We conclude by discussing the implications of our analysis in light of current debates on the ethics of digital health, and suggest measures to address the identified challenges.

[SUCCESSFUL AGING-A MULTI-FUNCTIONAL DIMENSION CONCEPT AN EMPHASIS ON THE END OF LIFE].

INTRODUCTION: The concept of "successful aging" as coined by Rowe and Kahan in the late nineties of the last century, came to describe a period of old age with multi-functional abilities. The functions are physical, cognitive and social, without progressive chronic diseases and without disabilities. There is a change in the concept of successful aging beyond the physical dimension (daily function (ADL) and cognitive function) which is based on objective performance indicators towards subjective indicators based on the patients' feelings and their quality of life. Successful aging moves from the limited bio-physical aspect to an overall view of bio-psycho-socio which means mental-emotional-behavioral aspects, social involvement, and also an element of spirituality and even end-of-life decisions. Successful aging will be measured by objective and subjective measures that include the patient's feelings and experiences. The idea is to include and see in successful aging not only the absence of morbidity and disability as seen by Rowe and Kahan, but to a multidimensional function that includes physical and cognitive, mental and emotional, social and spiritual parameters and a dimension of the end of life in making decisions according to the wishes and preferences of the person himself and his family.

Gastric Cancer Immune Subtypes and Prognostic Modeling: Insights from Aging-Related Gene Analysis.

Gastric cancer (GC) is highly heterogeneous and influenced by aging-related factors. This study aimed to improve individualized prognostic assessment of GC by identifying aging-related genes and subtypes. Immune scores of GC samples from GEO and TCGA databases were calculated using ESTIMATE and scored as high immune (IS_high) and low immune (IS_low). ssGSEA was used to analyze immune cell infiltration. Univariate Cox regression was employed to identify prognosis-related genes. LASSO regression analysis was used to construct a prognostic model. GSVA enrichment analysis was applied to determine pathways. CCK-8, wound healing, and Transwell assays tested the proliferation, migration, and invasion of the GC cell line (AGS). Cell cycle and aging were examined using flow cytometry, ß-galactosidase staining, and Western blotting. Two aging-related GC subtypes were identified. Subtype 2 was characterized as lower survival probability and higher risk, along with a more immune-responsive tumor microenvironment. Three genes (IGFBP5, BCL11B, and AKR1B1) screened from aging-related genes were used to establish a prognosis model. The AUC values of the model were greater than 0.669, exhibiting strong prognostic value. In vitro, IGFBP5 overexpression in AGS cells was found to decrease viability, migration, and invasion, alter the cell cycle, and increase aging biomarkers (SA-ß-galactosidase, p53, and p21). This analysis uncovered the immune characteristics of two subtypes and aging-related prognosis genes in GC. The prognostic model established for three aging-related genes (IGFBP5, BCL11B, and AKR1B1) demonstrated good prognosis performance, providing a foundation for personalized treatment strategies aimed at GC.

Two-Photon Microscopy for the Study of Tendons.

Two-photon microscopy has emerged as a potent tool for evaluating deep tissue cells and characterizing the alignment of the extracellular matrix (ECM) in various biological systems. This technique relies on nonlinear light-matter interactions to detect two distinct signals: the second harmonic generated (SHG) diffusion signal, which facilitates the visualization of collagen fibers and their orientation, and the near-infrared excitation signal for imaging ultraviolet excited autofluorescence. SHG imaging proves especially effective in visualizing collagen fibers due to the non-centrosymmetric crystalline structure of fibrillar collagen I. Given that tendons are matrix-rich tissues with a limited number of cells, their high collagen content makes them ideal candidates for analysis using two-photon microscopy. Consequently, two-photon microscopy offers a valuable means to analyze and characterize collagen abnormalities in tendons. Its application extends to studying tendon development, injuries, healing, and aging, enabling the comprehensive characterization of tendon cells and their interactions with the ECM under various conditions using two-photon microscopy tools. This protocol outlines the use of two-photon microscopy in tendon biology and presents an adapted methodology to achieve effective imaging and characterization of tendon cells during development and after injury. The method allows the utilization of thin microscopic sections to create a comprehensive image of the ECM within tendons and the cells that interact with this matrix. Most notably, the article showcases a technique to generate 3D images using two-photon microscopy in animal models.

Developmental priming of early cerebrovascular ageing: Implications across a lifetime.

INTRODUCTION: Neurological conditions such as Alzheimer's disease and stroke represent a substantial health burden to the world's ageing population. Cerebrovascular dysfunction is a key contributor to these conditions, affecting an individual's risk profile, age of onset, and severity of neurological disease. Recent data shows that early-life events, such as maternal health during pregnancy, birth weight and exposure to environmental toxins can 'prime' the vascular system for later changes. With age, blood vessels can become less flexible and more prone to damage. This can lead to reduced blood flow to the brain, which is associated with cognitive decline and an increased risk of stroke and other cerebrovascular diseases. These in turn increase the risk of vascular dementia and Alzheimer's disease. OBJECTIVES: We aim to explore how early life factors influence cerebrovascular health, ageing and disease. METHODS: We have reviewed recently published literature from epidemiological studies, clinical cases and basic research which explore mechanisms that contribute to cerebrovascular and blood-brain barrier dysfunction, with a particularly focus on those that assess contribution of early-life events or vascular priming to subsequent injury. RESULTS: Perinatal events have been linked to acute cerebrovascular dysfunction and long-term structural reorganisation. Systemic disease throughout the lifetime that produce inflammatory or oxidative stress may further sensitise the cerebrovasculature to disease and contribute to neurodegeneration. CONCLUSIONS: By identifying these early-life determinants and understanding their mechanisms, scientists aim to develop strategies for preventing or mitigating cerebrovascular ageing-related issues.

Cryptomphalus aspersa Egg Extract Protects against Human Stem Cell Stress-Induced Premature Senescence.

Cellular senescence is a tightly regulated pathophysiologic process and is caused by replicative exhaustion or external stressors. Since naturally derived bioactive compounds with anti-ageing properties have recently captured scientific interest, we analysed the anti-ageing and antioxidant efficacy of Cryptomphalus aspersa egg extract (CAEE). Its effects on stemness, wound-healing properties, antioxidant defense mechanisms, and DNA damage repair ability of Human Wharton's jelly mesenchymal stem cells (WJ-MSCs) were analysed. Our results revealed that CAEE fortifies WJ-MSCs stemness, which possibly ameliorates their wound-healing ability. Additionally, we show that CAEE possesses a strong antioxidant capacity as demonstrated by the elevation of the levels of the basic antioxidant molecule, GSH, and the induction of the NRF2, a major antioxidant regulator. In addition, CAEE alleviated cells' oxidative stress and therefore prevented stress-induced premature senescence (SIPS). Furthermore, we demonstrated that the prevention of SIPS could be mediated via the extract's ability to induce autophagy, as indicated by the elevation of the protein levels of all basic autophagic molecules and the increase in formation of autophagolysosomes in CAEE-treated WJ-MSCs. Moreover, CAEE-treated cells exhibited decreased Caveolin-1 levels. We propose that Cryptomphalus aspersa egg extract comprises bioactive compounds that can demonstrate strong antioxidant/anti-ageing effects by regulating the Caveolin-1-autophagy-senescence molecular axis.

Integrated Transcriptomic and Proteomic Study of the Mechanism of Action of the Novel Small-Molecule Positive Allosteric Modulator 1 in Targeting PAC1-R for the Treatment of D-Gal-Induced Aging Mice.

Small-molecule positive allosteric modulator 1 (SPAM1), which targets pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R), has been found to have a neuroprotective effect, and the underlying mechanism was explored in this study. First, using a D-galactose (D-gal)-induced aging mouse model, we confirmed that SPAM1 improves the structure of the hippocampal dentate gyrus and restores the number of neurons. Compared with D-gal model mice, SPAM1-treated mice showed up-regulated expression of Sirtuin 6 (SIRT6) and Lamin B1 and down-regulated expression of YinYang 1 (YY1) and p16. A similar tendency was observed in senescent RGC-5 cells induced by long-term culture, indicating that SPAM1 exhibits significant in vitro and in vivo anti-senescence activity in neurons. Then, using whole-transcriptome sequencing and proteomic analysis, we further explored the mechanism behind SPAM1's neuroprotective effects and found that SPAM is involved in the longevity-regulating pathway. Finally, the up-regulation of neurofilament light and medium polypeptides indicated by the proteomics results was further confirmed by Western blotting. These results help to lay a pharmacological network foundation for the use of SPAM1 as a potent anti-aging therapeutic drug to combat neurodegeneration with anti-senescence, neuroprotective, and nerve regeneration activity.

Reprogramming Chromosome Ends by Functional Histone Acetylation.

Cancers harness embryonic programs to evade aging and promote survival. Normally, sequences at chromosome ends called telomeres shorten with cell division, serving as a countdown clock to limit cell replication. Therefore, a crucial aspect of cancerous transformation is avoiding replicative aging by activation of telomere repair programs. Mouse embryonic stem cells (mESCs) activate a transient expression of the gene Zscan4, which correlates with chromatin de-condensation and telomere extension. Head and neck squamous cell carcinoma (HNSCC) cancers reactivate ZSCAN4, which in turn regulates the phenotype of cancer stem cells (CSCs). Our study reveals a new role for human ZSCAN4 in facilitating functional histone H3 acetylation at telomere chromatin. Next-generation sequencing indicates ZSCAN4 enrichment at telomere chromatin. These changes correlate with ZSCAN4-induced histone H3 acetylation and telomere elongation, while CRISPR/Cas9 knockout of ZSCAN4 leads to reduced H3 acetylation and telomere shortening. Our study elucidates the intricate involvement of ZSCAN4 and its significant contribution to telomere chromatin remodeling. These findings suggest that ZSCAN4 induction serves as a novel link between 'stemness' and telomere maintenance. Targeting ZSCAN4 may offer new therapeutic approaches to effectively limit or enhance the replicative lifespan of stem cells and cancer cells.

The Effect of Cold-Water Swimming on Energy Metabolism, Dynamics, and Mitochondrial Biogenesis in the Muscles of Aging Rats.

Our study aimed to explore the potential positive effects of cold water exercise on mitochondrial biogenesis and muscle energy metabolism in aging rats. The study involved 32 male and 32 female rats aged 15 months, randomly assigned to control sedentary animals, animals training in cold water at 5 ± 2 °C, or animals training in water at thermal comfort temperature (36 ± 2 °C). The rats underwent swimming training for nine weeks, gradually increasing the duration of the sessions from 2 min to 4 min per day, five days a week. The results demonstrated that swimming in thermally comfortable water improved the energy metabolism of aging rat muscles (increased metabolic rates expressed as increased ATP, ADP concentration, TAN (total adenine nucleotide) and AEC (adenylate energy charge value)) and increased mRNA and protein expression of fusion regulatory proteins. Similarly, cold-water swimming improved muscle energy metabolism in aging rats, as shown by an increase in muscle energy metabolites and enhanced mitochondrial biogenesis and dynamics. It can be concluded that the additive effect of daily activity in cold water influenced both an increase in the rate of energy metabolism in the muscles of the studied animals and an intensification of mitochondrial biogenesis and dynamics (related to fusion and fragmentation processes). Daily activity in warm water also resulted in an increase in the rate of energy metabolism in muscles, but at the same time did not cause significant changes in mitochondrial dynamics.

Ageing-Related Neurodegeneration and Cognitive Decline.

Neuropathological assessment was conducted on 1630 subjects, representing 5% of all the deceased that had been sent to the morgue of Uppsala University Hospital during a 15-year-long period. Among the 1630 subjects, 1610 were ≥41 years of age (range 41 to 102 years). Overall, hyperphosphorylated (HP) τ was observed in the brains of 98% of the 1610 subjects, and amyloid ß-protein (Aß) in the brains of 64%. The most common alteration observed was Alzheimer disease neuropathologic change (ADNC) (56%), followed by primary age-related tauopathy (PART) in 26% of the subjects. In 16% of the subjects, HPτ was limited to the locus coeruleus. In 14 subjects (<1%), no altered proteins were observed. In 3 subjects, only Aß was observed, and in 17, HPτ was observed in a distribution other than that seen in ADNC/PART. The transactive DNA-binding protein 43 (TDP43) associated with limbic-predominant age-related TDP encephalopathy (LATE) was observed in 565 (35%) subjects and α-synuclein (αS) pathology, i.e., Lewy body disease (LBD) or multi system atrophy (MSA) was observed in the brains of 21% of the subjects. A total of 39% of subjects with ADNC, 59% of subjects with PART, and 81% of subjects with HPτ limited to the locus coeruleus lacked concomitant pathologies, i.e., LATE-NC or LBD-NC. Of the 293 (18% of the 1610 subjects) subjects with dementia, 81% exhibited a high or intermediate level of ADNC. In 84% of all individuals with dementia, various degrees of concomitant alterations were observed; i.e., MIXED-NC was a common cause of dementia. A high or intermediate level of PART was observed in 10 subjects with dementia (3%), i.e., tangle-predominant dementia. No subjects exhibited only vascular NC (VNC), but in 17 subjects, severe VNC might have contributed to cognitive decline. Age-related tau astrogliopathy (ARTAG) was observed in 37% of the 1610 subjects and in 53% of those with dementia.

Accelerated Aging Induced by an Unhealthy High-Fat Diet: Initial Evidence for the Role of Nrf2 Deficiency and Impaired Stress Resilience in Cellular Senescence.

High-fat diets (HFDs) have pervaded modern dietary habits, characterized by their excessive saturated fat content and low nutritional value. Epidemiological studies have compellingly linked HFD consumption to obesity and the development of type 2 diabetes mellitus. Moreover, the synergistic interplay of HFD, obesity, and diabetes expedites the aging process and prematurely fosters age-related diseases. However, the underlying mechanisms driving these associations remain enigmatic. One of the most conspicuous hallmarks of aging is the accumulation of highly inflammatory senescent cells, with mounting evidence implicating increased cellular senescence in the pathogenesis of age-related diseases. Our hypothesis posits that HFD consumption amplifies senescence burden across multiple organs. To scrutinize this hypothesis, we subjected mice to a 6-month HFD regimen, assessing senescence biomarker expression in the liver, white adipose tissue, and the brain. Aging is intrinsically linked to impaired cellular stress resilience, driven by dysfunction in Nrf2-mediated cytoprotective pathways that safeguard cells against oxidative stress-induced senescence. To ascertain whether Nrf2-mediated pathways shield against senescence induction in response to HFD consumption, we explored senescence burden in a novel model of aging: Nrf2-deficient (Nrf2+/-) mice, emulating the aging phenotype. Our initial findings unveiled significant Nrf2 dysfunction in Nrf2+/- mice, mirroring aging-related alterations. HFD led to substantial obesity, hyperglycemia, and impaired insulin sensitivity in both Nrf2+/- and Nrf2+/+ mice. In control mice, HFD primarily heightened senescence burden in white adipose tissue, evidenced by increased Cdkn2a senescence biomarker expression. In Nrf2+/- mice, HFD elicited a significant surge in senescence burden across the liver, white adipose tissue, and the brain. We postulate that HFD-induced augmentation of senescence burden may be a pivotal contributor to accelerated organismal aging and the premature onset of age-related diseases.

5-Heptadecylresorcinol Improves Aging-Associated Hepatic Fatty Acid Oxidation Dysfunction via Regulating Adipose Sirtuin 3.

Aging-associated hepatic fatty acid (FA) oxidation dysfunction contributes to impaired adaptive thermogenesis. 5-Heptadecylresorcinol (AR-C17) is a prominent functional component of whole wheat and rye, and has been demonstrated to improve the thermogenic capacity of aged mice via the regulation of Sirt3. However, the effect of AR-C17 on aging-associated hepatic FA oxidation dysfunction remains unclear. Here, 18-month-old C57BL/6J mice were orally administered with AR-C17 at a dose of 150 mg/kg/day for 8 weeks. Systemic glucose and lipid metabolism, hepatic FA oxidation, and the lipolysis of white adipose tissues (WAT) were measured. The results showed that AR-C17 improved the hepatic FA oxidation, and especially acylcarnitine metabolism, of aged mice during cold stimulation, with the enhancement of systemic glucose and lipid metabolism. Meanwhile, AR-C17 improved the WAT lipolysis of aged mice, promoting hepatic acylcarnitine production. Furthermore, the adipose-specific Sirt3 knockout mice were used to investigate and verify the regulation mechanism of AR-C17 on aging-associated hepatic FA oxidation dysfunction. The results showed that AR-C17 failed to improve the WAT lipolysis and hepatic FA oxidation of aged mice in the absence of adipose Sirt3, indicating that AR-C17 might indirectly influence hepatic FA oxidation via regulating WAT Sirt3. Our findings suggest that AR-C17 might improve aging-associated hepatic FA oxidation dysfunction via regulating adipose Sirt3.

Polyphenolic Compounds: Orchestrating Intestinal Microbiota Harmony during Aging.

In the aging process, physiological decline occurs, posing a substantial threat to the physical and mental well-being of the elderly and contributing to the onset of age-related diseases. While traditional perspectives considered the maintenance of life as influenced by a myriad of factors, including environmental, genetic, epigenetic, and lifestyle elements such as exercise and diet, the pivotal role of symbiotic microorganisms had been understated. Presently, it is acknowledged that the intestinal microbiota plays a profound role in overall health by signaling to both the central and peripheral nervous systems, as well as other distant organs. Disruption in this bidirectional communication between bacteria and the host results in dysbiosis, fostering the development of various diseases, including neurological disorders, cardiovascular diseases, and cancer. This review aims to delve into the intricate biological mechanisms underpinning dysbiosis associated with aging and the clinical ramifications of such dysregulation. Furthermore, we aspire to explore bioactive compounds endowed with functional properties capable of modulating and restoring balance in this aging-related dysbiotic process through epigenetics alterations.

Nutrition and Aging in Dogs and Cats.

Aging is often associated with chronic inflammation and declining health. Both veterinarians and owners of aging dogs and cats are interested in nutritional solutions and strategies to prevent signs of age-related disease, increase longevity, and improve quality of life. Physiological decreases in muscle mass, decreased immunity, and a decrease in sense acuity are some of the changes often seen in otherwise healthy senior pets; however, there may also be an increase in risk for pathologies such as renal, cardiovascular, musculoskeletal, and neoplastic diseases. Aging may also lead to cognitive decline and even cognitive dysfunction. Some nutritional strategies that may be helpful with the prevention and treatment of age-related diseases include supplementation with ω3 polyunsaturated fatty acids and antioxidant nutrients that can help modulate inflammation and benefit osteoarthritis, renal disease, cancer, and more. Supplementation with medium-chain triglycerides shows promise in the treatment of canine cognitive dysfunction as these may be metabolized to ketone bodies that are utilized as an alternative energy source for the central nervous system. Additionally, a high intake of dietary phosphorus in soluble and bioavailable forms can lead to renal disease, which is of greater concern in senior pets. There are no published guidelines for nutritional requirements specific to senior pets and as a result, products marketed for senior dogs and cats are highly variable.

Association of 8-hydroxy-2'-deoxyguanosine with motoric cognitive risk in elderly Chinese people: RUGAO longevity and aging cross-sectional study.

BACKGROUND: Motor cognitive risk syndrome (MCR) represents a critical pre-dementia and disability state characterized by a combination of objectively measured slow walking speed and subjective memory complaints (SMCs). This study aims to identify risk factors for MCR and investigate the relationship between plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and MCR among Chinese community-dwelling elderly populations. METHODS: A total of 1312 participants were involved in this study based on the data of the Rugao Longevity and Aging Study (RuLAS). The MCR was characterized by SMCs and slow walking speed. The SCCs were defined as a positive answer to the question 'Do you feel you have more problems with memory than most?' in a 15-item Geriatric Depression Scale. Slow walking speed was determined by one standard deviation or more below the mean value of the patient's age and gender group. The plasma of 8-OHdG were measured by a technician in the biochemistry laboratory of the Rugao People's Hospital during the morning of the survey. RESULTS: The prevalence of MCR was found to be 7.9%. After adjusting for covariates, significant associations with MCR were observed in older age (OR 1.057; p = 0.018), history of cerebrovascular disease (OR 2.155; p = 0.010), and elevated 8-OHdG levels (OR 1.007; p = 0.003). CONCLUSIONS: This study indicated the elevated plasma 8-OHdG is significantly associated with increased MCR risk in the elderly, suggesting its potential as a biomarker for early detection and intervention in MCR. This finding underscores the importance of monitoring oxidative DNA damage markers in predicting cognitive and motor function declines, offering new avenues for research and preventive strategies in aging populations.