Ergothioneine boosts mitochondrial respiration and exercise performance via direct activation of MPST.

Ergothioneine (EGT) is a diet-derived, atypical amino acid that accumulates to high levels in human tissues. Reduced EGT levels have been linked to age-related disorders, including neurodegenerative and cardiovascular diseases, while EGT supplementation is protective in a broad range of disease and aging models in mice. Despite these promising data, the direct and physiologically relevant molecular target of EGT has remained elusive. Here we use a systematic approach to identify how mitochondria remodel their metabolome in response to exercise training. From this data, we find that EGT accumulates in muscle mitochondria upon exercise training. Proteome-wide thermal stability studies identify 3-mercaptopyruvate sulfurtransferase (MPST) as a direct molecular target of EGT; EGT binds to and activates MPST, thereby boosting mitochondrial respiration and exercise training performance in mice. Together, these data identify the first physiologically relevant EGT target and establish the EGT-MPST axis as a molecular mechanism for regulating mitochondrial function and exercise performance.

Targeting transcription factors through an IMiD independent zinc finger domain.

Immunomodulatory imide drugs (IMiDs) degrade specific C2H2 zinc finger degrons in transcription factors, making them effective against certain cancers. SALL4, a cancer driver, contains seven C2H2 zinc fingers in four clusters, including an IMiD degron in zinc finger cluster two (ZFC2). Surprisingly, IMiDs do not inhibit growth of SALL4 expressing cancer cells. To overcome this limit, we focused on a non-IMiD degron, SALL4 zinc finger cluster four (ZFC4). By combining AlphaFold and the ZFC4-DNA crystal structure, we identified a potential ZFC4 drug pocket. Utilizing an in silico docking algorithm and cell viability assays, we screened chemical libraries and discovered SH6, which selectively targets SALL4-expressing cancer cells. Mechanistic studies revealed that SH6 degrades SALL4 protein through the CUL4A/CRBN pathway, while deletion of ZFC4 abolished this activity. Moreover, SH6 led to significant 62% tumor growth inhibition of SALL4+ xenografts in vivo and demonstrated good bioavailability in pharmacokinetic studies. In summary, these studies represent a new approach for IMiD independent drug discovery targeting C2H2 transcription factors in cancer.

Path analysis of illness uncertainty and psychosocial adaptation of patients with Marfan syndrome.

AIMS: Marfan syndrome (MFS) is a genetic disorder that causes sudden or chronic cardiovascular problems, which can be fatal. Since MFS patients require regular close medical observation, it is important to understand the factors and pathways associated with psychosocial adaptation to the disease. This study aimed to identify the relationships among illness uncertainty, uncertainty appraisal, and psychosocial adaptation in MFS patients using path analysis. METHOD AND RESULTS: This descriptive cross-sectional survey study was conducted from October 2020 to March 2021, in compliance with STROBE guidelines. Using data from 179 participants aged older than 18 years, we constructed a hypothetical path model to identify determinants of illness uncertainty, uncertainty appraisal, and psychosocial adaptation. In the path analysis, disease severity, illness uncertainty, anxiety, and social support were significant factors influencing MFS patients' psychosocial adaptation. Disease severity and illness uncertainty exerted direct effects, while anxiety and social support exerted both direct and indirect (through illness uncertainty) effects. Finally, anxiety showed the greatest total effect. CONCLUSION: These findings are useful for enhancing MFS patients' psychosocial adaptation. Medical professionals should focus on managing disease severity, decreasing anxiety, and increasing social support.

Everyday Digital Literacy Questionnaire for Older Adults: Instrument Development and Validation Study.

BACKGROUND: The need for digital literacy in aging populations is increasing in the digitalizing society. Digital literacy involves the identification, evaluation, and communication of information through various digital devices or relevant programs. OBJECTIVE: The aims of this study were to develop an Everyday Digital Literacy Questionnaire (EDLQ), a digital literacy assessment scale, and subsequently evaluate its psychometric properties using a population of community-dwelling older adults in South Korea. METHODS: The EDLQ was developed using an instrument development design. A nationwide survey was conducted, and the study included 1016 community-dwelling older adults (age ≥60 years). To evaluate the psychometric properties, the participants were randomly divided into 2 groups (n=508 each), and the internal consistency (Cronbach α and McDonald ω), structural validity (exploratory factor analysis and confirmatory factor analysis), hypothesis-testing construct validity using the eHealth Literacy Scale (eHEALS), and measurement invariance were analyzed. RESULTS: Among the initial 30 items of the EDLQ, 22 items with a 3-factor solution had a total explained variance of 77%. The domains included "information and communication" (9 items), "content creation and management" (4 items), and "safety and security" (9 items). Confirmatory factor analysis was conducted with this 3-factor solution (χ2206=345.1; normed χ2206=1.7; comparative fit index=0.997; Tucker-Lewis index=0.997; root-mean-square error of approximation=0.036; standardized root-mean-square residual=0.050; composite reliability=0.903-0.959; average variance extracted=0.699-0.724; R2=0.616-0.773). Hypothesis-testing construct validity with the eHEALS revealed a strong correlation (r=0.75). Cronbach α and McDonald ω coefficients were .98 and 0.98, respectively. The fit indices for measurement invariance, including the configural, metric, and scalar invariance models, demonstrated a satisfactory fit to the data. Our findings suggest that the psychometric properties of the 22-item EDLQ are valid and reliable for assessing digital literacy among older Korean adults. CONCLUSIONS: In this study, we developed a digital literacy measure with strong psychometric properties that made it suitable for assessing the digital literacy of community-dwelling older adults in Korea. To broaden its applicability, however, further assessment of its feasibility for use with different languages and cultures is necessary. Moreover, more empirical research on digital literacy and related factors in older adults can facilitate the development of personalized digital health care services and educational interventions in the digital society.

Prevalence and associated factors of cognitive frailty in community-dwelling older adults: Results from the Korean longitudinal study of aging.

BACKGROUND: Cognitive frailty, a condition characterized by physical frailty with cognitive impairment, is emerging as a determinant of adverse health outcomes in older adults. However, its prevalence and correlation with associated factors are unknown in the aging population of Korea. OBJECTIVES: To estimate the prevalence of cognitive frailty and identify factors associated with it among older Korean adults. METHODS: A secondary analysis was performed using the Korean Longitudinal Study of Aging seventh survey dataset collected in 2018. Multinomial logistic regression analyses were conducted to examine the association between cognitive frailty and demographic, psychosocial, oral health and physical function factors. Individuals aged ≥65 years and without dementia were included (N = 1024). Participants were classified into four groups based on the presence or absence of physical frailty and mild cognitive impairment. This article is executed in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. RESULTS: The prevalence of cognitive frailty in the study sample was 11.2%. The results of multinomial logistic regression showed that advanced age, being female, lower education levels, heart disease, arthritis or rheumatoid arthritis, underweight, depression, non-social activity, poor oral health and functional limitation were significantly associated with cognitive frailty. CONCLUSIONS: Cognitive frailty is prevalent among community-dwelling older adults in Korea. The findings provide primary care providers with insights about effective strategies for identifying at-risk individuals and will guide the development of population-level interventions to prevent or delay the onset of physical frailty and cognitive impairment in older adults. IMPLICATIONS FOR PRACTICE: The findings provide practical information to healthcare providers for identifying cognitive frailty in older adults. The risk factors of cognitive frailty, such as psychosocial, oral health, and physical function factors, should be thoroughly monitored for older adults. Health personnel working in primary care have a critical role in identifying risk and beneficial factors and promoting preventative strategies that enhance health outcomes.

Irisin acts through its integrin receptor in a two-step process involving extracellular Hsp90α.

Exercise benefits the human body in many ways. Irisin is secreted by muscle, increased with exercise, and conveys physiological benefits, including improved cognition and resistance to neurodegeneration. Irisin acts via αV integrins; however, a mechanistic understanding of how small polypeptides like irisin can signal through integrins is poorly understood. Using mass spectrometry and cryo-EM, we demonstrate that the extracellular heat shock protein 90α (eHsp90α) is secreted by muscle with exercise and activates integrin αVß5. This allows for high-affinity irisin binding and signaling through an Hsp90α/αV/ß5 complex. By including hydrogen/deuterium exchange data, we generate and experimentally validate a 2.98 Å RMSD irisin/αVß5 complex docking model. Irisin binds very tightly to an alternative interface on αVß5 distinct from that used by known ligands. These data elucidate a non-canonical mechanism by which a small polypeptide hormone like irisin can function through an integrin receptor.

Comparison of cardiovascular disease risk in women with and without breast cancer: secondary data analysis with the 2014-2018 korean national health and nutrition examination survey.

BACKGROUND: Aging breast cancer survivors may be at an elevated risk of cardiovascular disease (CVD), but little is known about CVD risk assessment and breast cancer in Korean women. We hypothesized that Korean breast cancer survivors would have higher risks of future CVD within the next 10 years (i.e., Framingham Risk Score [FRS]) than women without cancer. OBJECTIVES: (1) To compare FRS-based CVD risks in women with and without breast cancer based on propensity score matching; and (2) To explore adiposity-related measures in relation to FRS in Korean women with breast cancer. METHODS: Using the cross-sectional data from the 2014-2018 Korean National Health and National Survey (KNHANES), we identified 136 women with breast cancer aged 30-74 years who had no other cancer and no CVD. The comparison group of 544 women with no cancer were selected by 1:4 nearest-neighbor propensity score matching based on breast cancer diagnosis. CVD risk was assessed by FRS based on multiple traditional risk factors (e.g., cholesterol, blood pressure, diabetes, and smoking). Adiposity was measured by physical examination, including body mass index (BMI) and waist-to-height ratio (WHtR). Physical activity and health behaviors were assessed by self-reports. RESULTS: Women with breast cancer (mean age of 57 years) had similar FRS levels at a low-risk category (< 10%) to women with no cancer (4.9% vs. 5.5%). Breast cancer survivors (mean 8.5 survival years) presented at significantly lower levels of total cholesterol, BMI, and WHtR (all p values < 0.05) than their counterpart. Within the breast cancer group, WHtR ≥ 0.5 was associated with higher FRS, compared to WHtR < 0.5. FRS was not different by survival < 5 years or ≥ 5 years after breast cancer diagnosis. CONCLUSIONS: FRS-based CVD risks were not different in Korean, mostly postmenopausal, women by breast cancer status. Whereas breast cancer survivors had even lower levels of lipid and adiposity measures than women without cancer, those values indicating borderline cardiometabolic risk suggest continued screening and management efforts for these aging women. Future studies are needed to examine longitudinal trajectories of CVD risk factors and CVD outcomes among Korean breast cancer survivors.

Association of Depressive Mood and Frailty With Mortality and Health Care Utilization: Korean National Cohort Study.

OBJECTIVES: To investigate the association of depressive mood and frailty with mortality and health care utilization (HCU) and identify the coexisting effect of depressive mood and frailty in older adults. DESIGN: A retrospective study using nationwide longitudinal cohort data. SETTING AND PARTICIPANTS: A total of 27,818 older adults age 66 years from the National Screening Program for Transitional Ages between 2007 and 2008, part of the National Health Insurance Service-Senior cohort. METHODS: Depressive mood and frailty were measured by the Geriatric Depression Scale and Timed Up and Go test, respectively. Outcomes were mortality and HCU, including long-term care services (LTCS), hospital admissions, and total length of stay (LOS) from the index date to December 31, 2015. Cox proportional hazards regression and zero-inflated negative binomial regression were performed to identify differences in outcomes by depressive mood and frailty. RESULTS: Participants with depressive mood and frailty represented 50.9% and 2.4%, respectively. The prevalence of mortality and LTCS use in the overall participants was 7.1% and 3.0%, respectively. More than 3 hospital admissions (36.7%) and total LOS above 15 days (53.2%) were the most common. Depressive mood was associated with LTCS use [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.05-1.42] and hospital admissions [incidence rate ratio (IRR) 1.05, 95% CI 1.02-1.08]. Frailty had associations with mortality risk (HR 1.96, 95% CI 1.44-2.68), LTCS use (HR 4.86, 95% CI 3.45-6.84), and LOS (IRR 1.30, 95% CI 1.06-1.60). The coexistence of depressive mood and frailty was associated with increased LOS (IRR 1.55, 95% CI 1.16-2.07). CONCLUSIONS AND IMPLICATIONS: Our findings highlight the need to focus on depressive mood and frailty to reduce mortality and HCU. Identifying combined problems in older adults may contribute to healthy aging by reducing adverse health outcomes and the burden of health care costs.

Lactate regulates cell cycle by remodelling the anaphase promoting complex.

Lactate is abundant in rapidly dividing cells owing to the requirement for elevated glucose catabolism to support proliferation1-6. However, it is not known whether accumulated lactate affects the proliferative state. Here we use a systematic approach to determine lactate-dependent regulation of proteins across the human proteome. From these data, we identify a mechanism of cell cycle regulation whereby accumulated lactate remodels the anaphase promoting complex (APC/C). Remodelling of APC/C in this way is caused by direct inhibition of the SUMO protease SENP1 by lactate. We find that accumulated lactate binds and inhibits SENP1 by forming a complex with zinc in the SENP1 active site. SENP1 inhibition by lactate stabilizes SUMOylation of two residues on APC4, which drives UBE2C binding to APC/C. This direct regulation of APC/C by lactate stimulates timed degradation of cell cycle proteins, and efficient mitotic exit in proliferative human cells. This mechanism is initiated upon mitotic entry when lactate abundance reaches its apex. In this way, accumulation of lactate communicates the consequences of a nutrient-replete growth phase to stimulate timed opening of APC/C, cell division and proliferation. Conversely, persistent accumulation of lactate drives aberrant APC/C remodelling and can overcome anti-mitotic pharmacology via mitotic slippage. In sum, we define a biochemical mechanism through which lactate directly regulates protein function to control the cell cycle and proliferation.

Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice.

Development of SARS-CoV-2 vaccines that protect vulnerable populations is a public health priority. Here, we took a systematic and iterative approach by testing several adjuvants and SARS-CoV-2 antigens to identify a combination that elicits antibodies and protection in young and aged mice. While demonstrating superior immunogenicity to soluble receptor-binding domain (RBD), RBD displayed as a protein nanoparticle (RBD-NP) generated limited antibody responses. Comparison of multiple adjuvants including AddaVax, AddaS03, and AS01B in young and aged mice demonstrated that an oil-in-water emulsion containing carbohydrate fatty acid monosulphate derivative (CMS:O/W) most effectively enhanced RBD-NP-induced cross-neutralizing antibodies and protection across age groups. CMS:O/W enhanced antigen retention in the draining lymph node, induced injection site, and lymph node cytokines, with CMS inducing MyD88-dependent Th1 cytokine polarization. Furthermore, CMS and O/W synergistically induced chemokine production from human PBMCs. Overall, CMS:O/W adjuvant may enhance immunogenicity and protection of vulnerable populations against SARS-CoV-2 and other infectious pathogens.

Gut microbial metabolism of 5-ASA diminishes its clinical efficacy in inflammatory bowel disease.

For decades, variability in clinical efficacy of the widely used inflammatory bowel disease (IBD) drug 5-aminosalicylic acid (5-ASA) has been attributed, in part, to its acetylation and inactivation by gut microbes. Identification of the responsible microbes and enzyme(s), however, has proved elusive. To uncover the source of this metabolism, we developed a multi-omics workflow combining gut microbiome metagenomics, metatranscriptomics and metabolomics from the longitudinal IBDMDB cohort of 132 controls and patients with IBD. This associated 12 previously uncharacterized microbial acetyltransferases with 5-ASA inactivation, belonging to two protein superfamilies: thiolases and acyl-CoA N-acyltransferases. In vitro characterization of representatives from both families confirmed the ability of these enzymes to acetylate 5-ASA. A cross-sectional analysis within the discovery cohort and subsequent prospective validation within the independent SPARC IBD cohort (n = 208) found three of these microbial thiolases and one acyl-CoA N-acyltransferase to be epidemiologically associated with an increased risk of treatment failure among 5-ASA users. Together, these data address a longstanding challenge in IBD management, outline a method for the discovery of previously uncharacterized gut microbial activities and advance the possibility of microbiome-based personalized medicine.

A nurse-led mHealth intervention to alleviate depressive symptoms in older adults living alone in the community: A quasi-experimental study.

BACKGROUND: The prevalence of geriatric depression has increased worldwide, becoming a major contributor to the burden of health care costs. Geriatric depression is difficult to detect in daily life because of its atypical presentation for each person. Therefore, there is an emerging need to develop personalised mHealth interventions for older adults with depression based on data from an ecological momentary assessment. OBJECTIVE: To develop and evaluate the effect of a nurse-led mHealth intervention of geriatric depression in older adults living alone. DESIGN: A quasi-experimental research design was used, and the study followed the transparent reporting of evaluations with a nonrandomised design statement. SETTING: The nurse-led mHealth intervention was developed and evaluated in a community senior centre in Seoul, Korea. PARTICIPANTS: Sixty-four older adults living alone with depressive symptoms were recruited between 1 October 2018 and 1 October 2019. METHODS: Study participants were randomly assigned to the intervention or control groups by drawing lots. In the intervention group, nurses repeatedly assessed older adults' depressive symptoms using an ecological momentary assessment via a mobile tablet. The intervention consisted of weekly sessions, which included (1) standardised mHealth device training, (2) a nurse-led mHealth programme, and (3) art activities. The control group received care as usual. Intra- and inter-group differences were evaluated using paired t-tests and analysis of covariance was used to assess subjective depression symptoms. A linear mixed-model was used to analyse the relationship between groups and momentary scores over time. RESULTS: The average age of the final sample was 76.2 years (SD = 6.06), 63.6 % (28/44) of whom were female. Compared with the control group (n = 23), the intervention group (n = 21) showed a decreased depression score (t = 4.041, p = .027). There was no statistical difference between the intervention and control groups based on traditional scales and the ecological momentary assessment. However, our data from the ecological momentary assessment captures clear fluctuating patterns across the days during the study, which traditional scales could not measure. CONCLUSIONS: Most of the older adults successfully participated in a nurse-led mHealth intervention that included multiple components of a non-pharmacological approach to address depression. Mental health nurses should perform critical roles to personalise mHealth activities considering the older adult's autonomy and supportive decision-making, specifically when using high-technological intervention. Future research should maximise the methodological and clinical advantage of an ecological momentary assessment of geriatric depression. REGISTRATION: Clinical Research Information Service number KCT0005073.

Decreasing patterns of depression in living alone across middle-aged and older men and women using a longitudinal mixed-effects model.

There is little evidence regarding the association between living arrangement and depression, and no studies have examined the age- and gender-specific differences in this association. The present study sought to examine the longitudinal changes in depression patterns between isolative living versus living in company among middle-aged and older men and women by obtaining data from waves 1-7 of the Korean Longitudinal Study of Aging (KloSA), which comprises a sample of persons at least 45 years of age in the Republic of Korea (2273 middle-aged and 1387 older men, 2805 middle aged and 1862 older women). Depression scores were based on the self-reported Center for Epidemiologic Studies Depression Scale (CES-D-10) short forms. Using mixed-effect linear regression models, we estimated depression patterns by living arrangement across age- and gender groups. Our findings from the mixed-effects model revealed that over a 14-year follow-up period, there were significant decreasing patterns of depression were among middle-aged men and women, and older men living alone compared to living with a spouse and living with others. However, living alone still had the highest depression compared to other living arrangement types. On the other hand, the depression of older women living alone changed to a level similar to those living with others during the follow-up period. In conclusion, these findings indicate that living alone significantly increases the risk of depression, but the risk decreases over time. Additionally, depression patterns by living arrangement proved to differ across age and gender groups.

BAF Complex Maintains Glioma Stem Cells in Pediatric H3K27M Glioma.

Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that are refractory to standard-of-care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape. To interrogate for epigenetic dependencies, we performed a CRISPR screen and show that patient-derived H3K27M-glioma neurospheres are dependent on core components of the mammalian BAF (SWI/SNF) chromatin remodeling complex. The BAF complex maintains glioma stem cells in a cycling, oligodendrocyte precursor cell-like state, in which genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacologic suppression, opposes proliferation, promotes progression of differentiation along the astrocytic lineage, and improves overall survival of patient-derived xenograft models. In summary, we demonstrate that therapeutic inhibition of the BAF complex has translational potential for children with H3K27M gliomas. SIGNIFICANCE: Epigenetic dysregulation is at the core of H3K27M-glioma tumorigenesis. Here, we identify the BRG1-BAF complex as a critical regulator of enhancer and transcription factor landscapes, which maintain H3K27M glioma in their progenitor state, precluding glial differentiation, and establish pharmacologic targeting of the BAF complex as a novel treatment strategy for pediatric H3K27M glioma. See related commentary by Beytagh and Weiss, p. 2730. See related article by Mo et al., p. 2906.

Covalent disruptor of YAP-TEAD association suppresses defective Hippo signaling.

The transcription factor TEAD, together with its coactivator YAP/TAZ, is a key transcriptional modulator of the Hippo pathway. Activation of TEAD transcription by YAP has been implicated in a number of malignancies, and this complex represents a promising target for drug discovery. However, both YAP and its extensive binding interfaces to TEAD have been difficult to address using small molecules, mainly due to a lack of druggable pockets. TEAD is post-translationally modified by palmitoylation that targets a conserved cysteine at a central pocket, which provides an opportunity to develop cysteine-directed covalent small molecules for TEAD inhibition. Here, we employed covalent fragment screening approach followed by structure-based design to develop an irreversible TEAD inhibitor MYF-03-69. Using a range of in vitro and cell-based assays we demonstrated that through a covalent binding with TEAD palmitate pocket, MYF-03-69 disrupts YAP-TEAD association, suppresses TEAD transcriptional activity and inhibits cell growth of Hippo signaling defective malignant pleural mesothelioma (MPM). Further, a cell viability screening with a panel of 903 cancer cell lines indicated a high correlation between TEAD-YAP dependency and the sensitivity to MYF-03-69. Transcription profiling identified the upregulation of proapoptotic BMF gene in cancer cells that are sensitive to TEAD inhibition. Further optimization of MYF-03-69 led to an in vivo compatible compound MYF-03-176, which shows strong antitumor efficacy in MPM mouse xenograft model via oral administration. Taken together, we disclosed a story of the development of covalent TEAD inhibitors and its high therapeutic potential for clinic treatment for the cancers that are driven by TEAD-YAP alteration.

Type D personality, cognitive illness perception, depression, approach coping, and self-management among older adults in long-term care hospitals: Structural equation modeling.

This study aimed to construct a structural equation model to explore the relationship between Type D personality, cognitive illness perception, depression, approach-coping, and self-management. The study was conducted at two long-term care hospitals with 300 or more beds in Korea. Participants were 287 older patients from whom data were collected from February 17 to March 10, 2021, using a structured questionnaire comprising items on the following variables: Type D personality, cognitive illness perception, depression, approach coping, and self-management. Type D personality (ß=-.601, p=.001), cognitive illness perception (ß =.692, p <.001), depression (ß =-.204, p =.011), and approach-coping (ß =.326, p <.001) explained 78.8% of the total variance of self-management, highlighting their impact on how patients accept and manage a disease and their relevance to the self-management of older adults in long-term care hospitals.

Benefits of sustained physical activity from middle age to early old age on quality of life in early old age.

This study aimed to examine changes in physical activity (PA) over time (2009-2017) in the same participants and to determine an association between changes in PA and health-related quality of life (HRQoL) in early older adults (n = 994) using data from the Korea Health Panel Survey. HRQoL was measured using the EuroQol system, and the amount of PA was grouped into four activity levels: remained inactive, became inactive, became active, and remained active. The association of changes in PA over 8 years with HRQoL was examined using logistic regression analysis while controlling for socioeconomic and behavioral factors. Total PA decreased from 1859.72 ± 1760.01 MET-minutes in 2009 to 1264.80 ± 1251.14 MET-minutes in 2017 (P < 0.001). In 2017, 142 (14.3%) remained inactive, whereas 419 (42.2%) remained active. Participants who remained inactive in early old age were more likely to be in the lowest 10% HRQoL of the sample (odds ratio = 1.95, 95% confidence interval = 1.09-3.48). These findings indicate that health education and promotion must be prioritized for middle-aged adults, who are relatively inactive, so that they increase their current PA and improve their HRQoL to maximize the benefits of PA in old age.

mRNA booster vaccination protects aged mice against the SARS-CoV-2 Omicron variant.

The SARS-CoV-2 Omicron variant evades vaccine-induced immunity. While a booster dose of ancestral mRNA vaccines effectively elicits neutralizing antibodies against variants, its efficacy against Omicron in older adults, who are at the greatest risk of severe disease, is not fully elucidated. Here, we evaluate multiple longitudinal immunization regimens of mRNA BNT162b2 to assess the effects of a booster dose provided >8 months after the primary immunization series across the murine lifespan, including in aged 21-month-old mice. Boosting dramatically enhances humoral and cell-mediated responses with evidence of Omicron cross-recognition. Furthermore, while younger mice are protected without a booster dose, boosting provides sterilizing immunity against Omicron-induced lung infection in aged 21-month-old mice. Correlational analyses reveal that neutralizing activity against Omicron is strongly associated with protection. Overall, our findings indicate age-dependent vaccine efficacy and demonstrate the potential benefit of mRNA booster immunization to protect vulnerable older populations against SARS-CoV-2 variants.

Incidence and predictors of multimorbidity among older adults in Korea: a 10-year cohort study.

BACKGROUND: Due to the rapid growth of the older adult population, multimorbidity has become a global concern for an aging society. Multimorbidity has been associated with poor health outcomes, including low quality of life and a high risk of mortality, resulting in an overload of healthcare systems. However, multimorbidity incidence and its related factors are poorly understood among older adults. This study aimed to determine whether sociodemographic characteristics, lifestyle, and psychosocial factors predict multimorbidity incidence among older adults in Korea. METHODS: This longitudinal study used the Korean Longitudinal Study of Aging (KLoSA) dataset from 2008 to 2018. The KLoSA is a panel survey of nationally representative samples aimed at providing data for developing socioeconomic policies for the increasing aging population in Korea. The study sample included 1967 older adults aged 65 years and over who had none or one of the chronic diseases at the baseline in 2008. Multimorbidity incidence was defined as the co-existence of two or more chronic diseases among 12 doctor-diagnosed diseases based on self-reports. Cox's proportional hazards models were used to identify significant predictors of multimorbidity incidence over a 10-year follow-up period. RESULTS: Among 1967 respondents (female 54.5%, mean age 72.94), 625 (31.8%) incidents of multimorbidity were reported, contributing to 47.5 incidents per 1000 people after 10 years of follow-up. Low levels of social interaction, obesity, past smoking habits, and current or past drinking habits were identified as significant predictors of multimorbidity incidence among older adults in Korea. CONCLUSIONS: This study identified older adults at high risk for multimorbidity incidence. These groups require more attention from health care providers in the course of chronic disease monitoring and management. Specific interventions and health policies to promote social interaction and a healthy lifestyle are essential to delay multimorbidity incidence. This longitudinal approach will contribute to developing preventive strategies to reduce the incidence of multimorbidity among older adults.