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.

BIN1 knockdown rescues systolic dysfunction in aging male mouse hearts.

Cardiac dysfunction is a hallmark of aging in humans and mice. Here we report that a two-week treatment to restore youthful Bridging Integrator 1 (BIN1) levels in the hearts of 24-month-old mice rejuvenates cardiac function and substantially reverses the aging phenotype. Our data indicate that age-associated overexpression of BIN1 occurs alongside dysregulated endosomal recycling and disrupted trafficking of cardiac CaV1.2 and type 2 ryanodine receptors. These deficiencies affect channel function at rest and their upregulation during acute stress. In vivo echocardiography reveals reduced systolic function in old mice. BIN1 knockdown using an adeno-associated virus serotype 9 packaged shRNA-mBIN1 restores the nanoscale distribution and clustering plasticity of ryanodine receptors and recovers Ca2+ transient amplitudes and cardiac systolic function toward youthful levels. Enhanced systolic function correlates with increased phosphorylation of the myofilament protein cardiac myosin binding protein-C. These results reveal BIN1 knockdown as a novel therapeutic strategy to rejuvenate the aging myocardium.

Aging-related defects in macrophage function are driven by MYC and USF1 transcriptional programs.

Macrophages are central innate immune cells whose function declines with age. The molecular mechanisms underlying age-related changes remain poorly understood, particularly in human macrophages. We report a substantial reduction in phagocytosis, migration, and chemotaxis in human monocyte-derived macrophages (MDMs) from older (>50 years old) compared with younger (18-30 years old) donors, alongside downregulation of transcription factors MYC and USF1. In MDMs from young donors, knockdown of MYC or USF1 decreases phagocytosis and chemotaxis and alters the expression of associated genes, alongside adhesion and extracellular matrix remodeling. A concordant dysregulation of MYC and USF1 target genes is also seen in MDMs from older donors. Furthermore, older age and loss of either MYC or USF1 in MDMs leads to an increased cell size, altered morphology, and reduced actin content. Together, these results define MYC and USF1 as key drivers of MDM age-related functional decline and identify downstream targets to improve macrophage function in aging.

Evidence of a pan-tissue decline in stemness during human aging.

Despite their biological importance, the role of stem cells in human aging remains to be elucidated. In this work, we applied a machine learning methodology to GTEx transcriptome data and assigned stemness scores to 17,382 healthy samples from 30 human tissues aged between 20 and 79 years. We found that ~60% of the studied tissues exhibit a significant negative correlation between the subject's age and stemness score. The only significant exception was the uterus, where we observed an increased stemness with age. Moreover, we observed that stemness is positively correlated with cell proliferation and negatively correlated with cellular senescence. Finally, we also observed a trend that hematopoietic stem cells derived from older individuals might have higher stemness scores. In conclusion, we assigned stemness scores to human samples and show evidence of a pan-tissue loss of stemness during human aging, which adds weight to the idea that stem cell deterioration may contribute to human aging.

Blood-based biological ageing and red cell distribution width are associated with prevalent Parkinson's disease: findings from a large Italian population cohort.

Background: Aging clocks tag the actual underlying age of an organism and its discrepancy with chronological age and have been reported to predict incident disease risk in the general population. However, the relationship with neurodegenerative risk and in particular with Parkinson's Disease (PD) remains unclear, with few discordant findings reporting associations with both incident and prevalent PD risk. Objective: To clarify this relationship, we computed a common aging clock based on blood markers and tested the resulting discrepancy with chronological age (ΔPhenoAge) for association with both incident and prevalent PD risk. Methods: In a large Italian population cohort - the Moli-sani study (N=23,437; age ≥ 35 years; 52% women) - we carried out both Cox Proportional Hazards regressions modelling ΔPhenoAge as exposure and incident PD as outcome, and linear models testing prevalent PD as exposure and ΔPhenoAge as outcome. All models were incrementally adjusted for age, sex, education level completed and other risk/protective factors previously associated with PD risk in the same cohort (prevalent dysthyroidism, hypertension, diabetes, use of oral contraceptives, exposure to paints, daily coffee intake and cigarette smoking). Results: No significant association between incident PD risk (209 cases, median (IQR) follow-up time 11.19 (2.03) years) and PhenoAging was observed (Hazard Ratio [95% Confidence Interval] = 0.98 [0.71; 1.37]). However, a small but significant increase of ΔPhenoAge was observed in prevalent PD cases vs healthy subjects (ß (Standard Error) = 1.39 (0.70)). An analysis of each component biomarker of PhenoAge revealed a significant positive association of prevalent PD status with red cell distribution width (RDW; ß (SE) = 0.46 (0.18)). All the remaining markers did not show any significant evidence of association. Conclusion: The reported evidence highlights systemic effects of prevalent PD status on biological aging and red cell distribution width. Further cohort and functional studies may help shedding a light on the related pathways altered at the organism level in prevalent PD, like red cells variability, inflammatory and oxidative stress mechanisms.

[Alcohol Abstinence and Accelerated Biological Aging Among Middle-Aged and Older Adults: Evidence From the UK Biobank]. / ä¸­è€å¹´ç¾¤ä½“é ’ç²¾æˆ’æ–­ä¸Žç”Ÿç‰©è¡°è€åŠ é€Ÿçš„å ³ç³»ï¼šåŸºäºŽè‹±å›½ç”Ÿç‰©é“¶è¡Œæ•°æ®åº“çš„ç ”ç©¶.

Objective: To investigate the longitudinal association between alcohol abstinence and accelerated biological aging among middle-aged and older adults and to explore the potential effect modifiers influencing the association. Methods: Utilizing the clinico-biochemical and anthropometric data from the baseline and first repeat survey of the UK Biobank (UKB), we employed the Klemera and Doubal method (KDM) to construct the biological age (BA) and calculate BA acceleration. Change analysis based on multivariate linear regression models was employed to explore the association between changes in alcohol abstinence and changes in BA acceleration. Age, sex, smoking status, tea and coffee consumption, and body mass index were considered as the stratification factors for conducting stratified analysis. Results: A total of 5 412 participants were included. Short-term alcohol abstinence (ß=1.00, 95% confidence interval [CI]: 0.15-1.86) was found to accelerate biological aging when compared to consistent never drinking, while long-term abstinence (ß=-0.20, 95% CI: -1.12-0.71) did not result in a significant acceleration of biological aging. Body mass index may be a potential effect modifier. Conclusion: Short-term alcohol abstinence was associated with accelerated biological aging, but the effect gradually diminishes over extended periods of abstinence.

[Identification of Osteoarthritis Inflamm-Aging Biomarkers by Integrating Bioinformatic Analysis and Machine Learning Strategies and the Clinical Validation]. / ç”Ÿç‰©ä¿¡æ¯å­¦å’Œæœºå™¨å­¦ä¹ ç­–ç•¥è¯†åˆ«éª¨å ³èŠ‚ç‚Žç‚Žæ€§è¡°è€ç”Ÿç‰©æ ‡å¿—ç‰©ä¸Žä¸´åºŠéªŒè¯.

Objective: To identify inflamm-aging related biomarkers in osteoarthritis (OA). Methods: Microarray gene profiles of young and aging OA patients were obtained from the Gene Expression Omnibus (GEO) database and aging-related genes (ARGs) were obtained from the Human Aging Genome Resource (HAGR) database. The differentially expressed genes of young OA and older OA patients were screened and then intersected with ARGs to obtain the aging-related genes of OA. Enrichment analysis was performed to reveal the potential mechanisms of aging-related markers in OA. Three machine learning methods were used to identify core senescence markers of OA and the receiver operating characteristic (ROC) curve was used to assess their diagnostic performance. Peripheral blood mononuclear cells were collected from clinical OA patients to verify the expression of senescence-associated secretory phenotype (SASP) factors and senescence markers. Results: A total of 45 senescence-related markers were obtained, which were mainly involved in the regulation of cellular senescence, the cell cycle, inflammatory response, etc. Through the screening with the three machine learning methods, 5 core senescence biomarkers, including FOXO3, MCL1, SIRT3, STAG1, and S100A13, were obtained. A total of 20 cases of normal controls and 40 cases of OA patients, including 20 cases in the young patient group and 20 in the elderly patient group, were enrolled. Compared with those of the young patient group, C-reactive protein (CRP), interleukin (IL)-6, and IL-1ß levels increased and IL-4 levels decreased in the elderly OA patient group (P<0.01); FOXO3, MCL1, and SIRT3 mRNA expression decreased and STAG1 and S100A13 mRNA expression increased (P<0.01). Pearson correlation analysis demonstrated that the selected markers were associated with some indicators, including erythrocyte sedimentation rate (ESR), IL-1ß, IL-4, CRP, and IL-6. The area under the ROC curve of the 5 core aging genes was always greater than 0.8 and the C-index of the calibration curve in the nomogram prediction model was 0.755, which suggested the good calibration ability of the model. Conclusion: FOXO3, MCL1, SIRT3, STAG1, and S100A13 may serve as novel diagnostic biomolecular markers and potential therapeutic targets for OA inflamm-aging.

Managing multiple sclerosis in individuals aged 55 and above: a comprehensive review.

Multiple Sclerosis (MS) management in individuals aged 55 and above presents unique challenges due to the complex interaction between aging, comorbidities, immunosenescence, and MS pathophysiology. This comprehensive review explores the evolving landscape of MS in older adults, including the increased incidence and prevalence of MS in this age group, the shift in disease phenotypes from relapsing-remitting to progressive forms, and the presence of multimorbidity and polypharmacy. We aim to provide an updated review of the available evidence of disease-modifying treatments (DMTs) in older patients, including the efficacy and safety of existing therapies, emerging treatments such as Bruton tyrosine kinase (BTKs) inhibitors and those targeting remyelination and neuroprotection, and the critical decisions surrounding the initiation, de-escalation, and discontinuation of DMTs. Non-pharmacologic approaches, including physical therapy, neuromodulation therapies, cognitive rehabilitation, and psychotherapy, are also examined for their role in holistic care. The importance of MS Care Units and advance care planning are explored as a cornerstone in providing patient-centric care, ensuring alignment with patient preferences in the disease trajectory. Finally, the review emphasizes the need for personalized management and continuous monitoring of MS patients, alongside advocating for inclusive study designs in clinical research to improve the management of this growing patient demographic.

Associations Between Age at Menopause, Vascular Risk, and 3-Year Cognitive Change in the Canadian Longitudinal Study on Aging.

BACKGROUND AND OBJECTIVES: Mounting evidence supports sex differences in Alzheimer disease (AD) risk. Vascular and hormonal factors may together contribute to AD risk in female adults. We investigated whether age at menopause, vascular risk, and history of hormone therapy (HT) containing estrogens together influence cognition over a 3-year follow-up period. We hypothesized that earlier menopause and elevated vascular risk would have a synergistic association with lower cognitive scores at follow-up and that HT containing estrogens would attenuate this synergistic association to preserve cognition. METHODS: We used data from postmenopausal female participants and age-matched male participants in the Canadian Longitudinal Study on Aging. Vascular risk was calculated using a summary score of elevated blood pressure, antihypertensive medications, elevated low-density lipoprotein cholesterol, diabetes, smoking, and obesity. Cognition was measured with a global cognitive composite at baseline and 3-year follow-up. Linear models tested independent and interactive associations of age at menopause, vascular risk, and HT history with cognition at 3-year follow-up, adjusting for baseline cognition, baseline age, years of education, and test language (English/French). RESULTS: We included 8,360 postmenopausal female participants (mean age at baseline = 65.0 ± 8.53 years, mean age at menopause = 50.1 ± 4.62 years) and 8,360 age-matched male participants for comparison. There was an interaction between age at menopause and vascular risk, such that earlier menopause and higher vascular risk were synergistically associated with lower cognitive scores at follow-up (ß = 0.013, 95% CI 0.001-0.025, p = 0.03). In stratified analyses, vascular risk was associated with lower cognitive scores in female participants with earlier menopause (menopausal ages 35-48 years; ß = -0.044, 95% CI -0.066 to -0.022, p < 0.001), but not average (ages 49-52 years; ß = -0.007, 95% CI -0.027 to 0.012, p = 0.46) or later menopause (ages 53-65 years; ß = 0.003, 95% CI -0.020 to 0.025, p = 0.82). The negative association of vascular risk with cognition in female participants with earlier menopause was stronger than the equivalent association in age-matched male participants. HT history did not further modify the synergistic association of age at menopause and vascular risk with follow-up cognition (ß = -0.005, 95% CI -0.032 to 0.021, p = 0.69). DISCUSSION: Endocrine and vascular processes may synergistically contribute to increased risk of cognitive decline in female adults. These findings have implications for the development of sex-specific dementia prevention strategies.

Age-Dependent Changes in the Production of Mitochondrial Reactive Oxygen Species in Human Skeletal Muscle.

A decrease in muscle mass and its functionality (strength, endurance, and insulin sensitivity) is one of the integral signs of aging. One of the triggers of aging is an increase in the production of mitochondrial reactive oxygen species. Our study was the first to examine age-dependent changes in the production of mitochondrial reactive oxygen species related to a decrease in the proportion of mitochondria-associated hexokinase-2 in human skeletal muscle. For this purpose, a biopsy was taken from m. vastus lateralis in 10 young healthy volunteers and 70 patients (26-85 years old) with long-term primary arthrosis of the knee/hip joint. It turned out that aging (comparing different groups of patients), in contrast to inactivity/chronic inflammation (comparing young healthy people and young patients), causes a pronounced increase in peroxide production by isolated mitochondria. This correlated with the age-dependent distribution of hexokinase-2 between mitochondrial and cytosolic fractions, a decrease in the rate of coupled respiration of isolated mitochondria and respiration when stimulated with glucose (a hexokinase substrate). It is discussed that these changes may be caused by an age-dependent decrease in the content of cardiolipin, a potential regulator of the mitochondrial microcompartment containing hexokinase. The results obtained contribute to a deeper understanding of age-related pathogenetic processes in skeletal muscles and open prospects for the search for pharmacological/physiological approaches to the correction of these pathologies.

Evolution of Longevity in Tetrapods: Safety Is More Important than Metabolism Level.

Various environmental morphological and behavioral factors can determine the longevity of representatives of various taxa. Long-lived species develop systems aimed at increasing organism stability, defense, and, ultimately, lifespan. Long-lived species to a different extent manifest the factors favoring longevity (gerontological success), such as body size, slow metabolism, activity of body's repair and antioxidant defense systems, resistance to toxic substances and tumorigenesis, and presence of neotenic features. In continuation of our studies of mammals, we investigated the characteristics that distinguish long-lived ectotherms (crocodiles and turtles) and compared them with those of other ectotherms (squamates and amphibians) and endotherms (birds and mammals). We also discussed mathematical indicators used to assess the predisposition to longevity in different species, including standard indicators (mortality rate, maximum lifespan, coefficient of variation of lifespan) and their derivatives. Evolutionary patterns of aging are further explained by the protective phenotypes and life history strategies. We assessed the relationship between the lifespan and various studied factors, such as body size and temperature, encephalization, protection of occupied ecological niches, presence of protective structures (for example, shells and osteoderms), and environmental temperature, and the influence of these factors on the variation of the lifespan as a statistical parameter. Our studies did not confirm the hypothesis on the metabolism level and temperature as the most decisive factors of longevity. It was found that animals protected by shells (e.g., turtles with their exceptional longevity) live longer than species that have poison or lack such protective adaptations. The improvement of defense against external threats in long-lived ectotherms is consistent with the characteristics of long-lived endotherms (for example, naked mole-rats that live in underground tunnels, or bats and birds, whose ability to fly is one of the best defense mechanisms).

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 Between Composite Dietary Antioxidant Index and Cognitive Function Among Aging Americans from NHANES 2011-2014.

Background: Antioxidant diets are considered to be protective factors for cognitive function. However, comprehensive measures of antioxidant diets are lacking. Objective: To examine the association between the Composite Dietary Antioxidant Index (CDAI) and cognitive function in the elderly. Methods: This cross-sectional study included a total of 2,456 participants (≥60 years old) from NHANES 2011-2014. Calculation of CDAI based on 6 minerals and vitamins (manganese, selenium, zinc, vitamins A, C, and E). Cognitive function was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning sub-test, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). We also created a composite cognitive z-score to represent global cognition. The statistical analyses we used included multiple linear regression analyses, subgroup analyses, curve-fitting analyses, and threshold effects analyses. Results: After controlling for demographic characteristics, lifestyle factors, and disease history, multivariate linear regression analyses showed that increased CDAI was positively associated with scores on global cognitive function and each cognitive domain (p < 0.05), with subgroup analyses suggesting that this association was more pronounced in stroke patients (p for interaction < 0.05). Curve-fitting analyses and threshold effect analyses showed saturation effects between CDAI and CREAD Test, AFT, and composite Z-score, and an inverted U-shaped relationship with DSST, with inflection points of -1.89, 0.79, 1.13, and 1.77, respectively. Conclusions: Our findings support that higher levels of CDAI are correlated with significantly elevated cognitive function. Maintaining CDAI in an appropriate range may contribute to cognitive health in elderly.

Targeting aging and age-related diseases with vaccines.

Aging is a major risk factor for numerous chronic diseases. Vaccination offers a promising strategy to combat these age-related diseases by targeting specific antigens and inducing immune responses. Here, we provide a comprehensive overview of recent advances in vaccine-based interventions targeting these diseases, including Alzheimer's disease, type II diabetes, hypertension, abdominal aortic aneurysm, atherosclerosis, osteoarthritis, fibrosis and cancer, summarizing current approaches for identifying disease-associated antigens and inducing immune responses against these targets. Further, we reflect on the recent development of vaccines targeting senescent cells, as a strategy for more broadly targeting underlying causes of aging and associated pathologies. In addition to highlighting recent progress in these areas, we discuss important next steps to advance the therapeutic potential of these vaccines, including improving and robustly demonstrating efficacy in human clinical trials, as well as rigorously evaluating the safety and long-term effects of these vaccine strategies.

Aging-induced MCPH1 translocation activates necroptosis and impairs hematopoietic stem cell function.

DNA damage contributes to the aging of hematopoietic stem cells (HSCs), yet the underlying molecular mechanisms are not fully understood. In this study, we identified a heterogeneous functional role of microcephalin (MCPH1) in the nucleus and cytoplasm of mouse HSCs. In the nucleus, MCPH1 maintains genomic stability, whereas in the cytoplasm, it prevents necroptosis by binding with p-RIPK3. Aging triggers MCPH1 translocation from cytosol to nucleus, reducing its cytoplasmic retention and leading to the activation of necroptosis and deterioration of HSC function. Mechanistically, we found that KAT7-mediated lysine acetylation within the NLS motif of MCPH1 in response to DNA damage facilitates its nuclear translocation. Targeted mutation of these lysines inhibits MCPH1 translocation and, consequently, compromises necroptosis. The dysfunction of necroptosis signaling, in turn, improves the function of aged HSCs. In summary, our findings demonstrate that DNA damage-induced redistribution of MCPH1 promotes HSC aging and could have broader implications for aging and aging-related diseases.

Exposure to ambient air pollution and cognitive function: an analysis of the English Longitudinal Study of Ageing cohort.

BACKGROUND: An increasing number of studies suggest adverse effects of exposure to ambient air pollution on cognitive function, but the evidence is still limited. We investigated the associations between long-term exposure to air pollutants and cognitive function in the English Longitudinal Study of Ageing (ELSA) cohort of older adults. METHODS: Our sample included 8,883 individuals from ELSA, based on a nationally representative study of people aged ≥ 50 years, followed-up from 2002 until 2017. Exposure to air pollutants was modelled by the CMAQ-urban dispersion model and assigned to the participants' residential postcodes. Cognitive test scores of memory and executive function were collected biennially. The associations between these cognitive measures and exposure to ambient concentrations of NO2, PM10, PM2.5 and ozone were investigated using mixed-effects models adjusted for time-varying age, physical activity and smoking status, as well as baseline gender and level of education. RESULTS: Increasing long-term exposure per interquartile range (IQR) of NO2 (IQR: 13.05 µg/m3), PM10 (IQR: 3.35 µg/m3) and PM2.5 (IQR: 2.7 µg/m3) were associated with decreases in test scores of composite memory by -0.10 (95% confidence interval [CI]: -0.14, -0.07), -0.02 [-0.04, -0.01] and -0.08 [-0.11, -0.05], respectively. The same increases in NO2, PM10 and PM2.5 were associated with decreases in executive function score of -0.31 [-0.38, -0.23], -0.05 [-0.08, -0.02] and -0.16 [-0.22, -0.10], respectively. The association with ozone was inverse across both tests. Similar results were reported for the London-dwelling sub-sample of participants. CONCLUSIONS: The present study was based on a long follow-up with several repeated measurements per cohort participant and long-term air pollution exposure assessment at a fine spatial scale. Increasing long-term exposure to NO2, PM10 and PM2.5 was associated with a decrease in cognitive function in older adults in England. This evidence can inform policies related to modifiable environmental exposures linked to cognitive decline.

Molecular Mechanism of Resveratrol and Its Therapeutic Potential on Female Infertility.

Resveratrol is a polyphenol present in various plant sources. Studies have reported numerous potential health benefits of resveratrol, exhibiting anti-aging, anti-inflammatory, anti-microbial, and anti-carcinogenic activity. Due to the reported effects, resveratrol is also being tested in reproductive disorders, including female infertility. Numerous cellular, animal, and even human studies were performed with a focus on the effect of resveratrol on female infertility. In this review, we reviewed some of its molecular mechanisms of action and summarized animal and human studies regarding resveratrol and female infertility, with a focus on age-related infertility, polycystic ovary syndrome, and endometriosis.

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.

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.

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.