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Abstract: McGrath, R, McGrath, BM, Jurivich, D, Knutson, P, Mastrud, M, Singh, B, and Tomkinson, GR. Collective weakness is associated with time to mortality in Americans. J Strength Cond Res 38(7): e398-e404, 2024-Using new weakness cutpoints individually may help estimate time to mortality, but their collective use could improve value. We sought to determine the associations of (a) each absolute and body size normalized cut point and (b) collective weakness on time to mortality in Americans. The analytic sample included 14,178 subjects aged ≥50 years from the 2006-2018 waves of the Health and Retirement Study. Date of death was confirmed from the National Death Index. Handgrip dynamometry measured handgrip strength (HGS). Men were categorized as weak if their HGS was <35.5 kg (absolute), <0.45 kg·kg -1 (body mass normalized), or <1.05 kg·kg -1 ·m -2 (body mass index [BMI] normalized). Women were classified as weak if their HGS was <20.0 kg, <0.337 kg·kg -1 , or <0.79 kg·kg -1 ·m -2 . Collective weakness categorized persons as below 1, 2, or all 3 cutpoints. Cox proportional hazard regression models were used for analyses. Subject values below each absolute and normalized cutpoint for the 3 weakness parameters had a higher hazard ratio for early all-cause mortality: 1.45 (95% confidence interval [CI]: 1.36-1.55) for absolute weakness, 1.39 (CI: 1.30-1.49) for BMI normalized weakness, and 1.33 (CI: 1.24-1.43) for body mass normalized weakness. Those below 1, 2, or all 3 weakness cut points had a 1.37 (CI: 1.26-1.50), 1.47 (CI: 1.35-1.61), and 1.69 (CI: 1.55-1.84) higher hazard for mortality, respectively. Weakness determined by a composite measure of absolute and body size adjusted strength capacity provides robust prediction of time to mortality, thus potentially informing sports medicine and health practitioner discussions about the importance of muscle strength during aging., (Copyright © 2024 National Strength and Conditioning Association.)

Accurate prediction of biological age can inform public health measures to extend healthy lifespans and reduce chronic conditions. Multiple theoretical models and methods have been developed; however, their applicability and accuracy are still not extensive. Here, we report Differential Aging and Health Index (DAnHI), a novel measure of age deviation, developed using physical and serum biomarkers from four million individuals in Korea's National Health Screening Program. Participants were grouped into aging statuses (< 26 vs. ≥ 26, < 27 vs. ≥ 27, …, < 75 vs. ≥ 75 years) as response variables in a binary logistic regression model with thirteen biomarkers as independent variables. DAnHI for each individual was calculated as the weighted mean of their relative probabilities of being classified into each older age status, based on model ages ranging from 26 to 75. DAnHI in our large study population showed a steady increase with the increase in age and was positively associated with death after adjusting for chronological age. However, the effect size of DAnHI on the risk of death varied according to the age group and sex. The hazard ratio was highest in the 50-59-year age group and then decreased as the individuals aged. This study demonstrates that routine health check-up biomarkers can be integrated into a quantitative measure for predicting aging-related health status and death via appropriate statistical models and methodology. Our DAnHI-based results suggest that the same level of aging-related health status does not indicate the same degree of risk for death., (© 2024. The Author(s).)

Background: Weakness can be operationalized with several thresholds, which in turn, could impact associations with cognitive impairment when considering obesity status., Objective: We examined the associations of absolute, normalized, and collective weakness thresholds on future cognitive impairment by obesity status in older adults., Methods: We performed a secondary data analysis on the 2006-2018 waves of the Health and Retirement Study. A spring-type dynamometer collected handgrip strength (HGS). Males were categorized weak if their HGS was <35.5-kg (absolute), <0.45-kg/kg (body mass normalized), or <1.05-kg/kg/m 2 (body mass index (BMI) normalized), while females were defined as weak if their HGS was <20.0-kg, <0.337-kg/kg, or <0.79-kg/kg/m 2 . The modified Telephone Interview of Cognitive Status examined cognitive function. Persons scoring ≤10 had a cognitive impairment. Obesity was categorized as BMI ≥30 kg/m 2 ., Results: We included 7,532 and 3,584 persons aged ≥65-years living without and with obesity, respectively. Those without obesity but beneath the absolute weakness threshold had 1.54 (95% confidence interval (CI): 1.24-1.91) greater odds for future cognitive impairment. Persons with obesity and beneath each threshold also had greater odds for future cognitive impairment: 1.89 (95% CI: 1.28-2.78) for absolute, 2.17 (95% CI: 1.02-4.62) for body mass normalized, and 1.75 (95% CI: 1.10-2.80) for BMI normalized. Older Americans without obesity but underneath all the weakness thresholds had 1.32 (95% CI: 1.00-1.74) greater odds for impairment in cognitive function, while persons with obesity had 2.76 (95% CI: 1.29-5.93) greater odds., Conclusions: There should be consideration for how body size and different weakness thresholds may influence future cognitive outcomes., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

The upper respiratory tract (nasopharynx or NP) is the first site of influenza replication, allowing the virus to disseminate to the lower respiratory tract or promoting community transmission. The host response in the NP regulates an intricate balance between viral control and tissue pathology. The hyper-inflammatory responses promote epithelial injury, allowing for increased viral dissemination and susceptibility to secondary bacterial infections. However, the pathologic contributors to influenza upper respiratory tissue pathology are incompletely understood. In this study, we investigated the role of interleukin IL-17 recetor A (IL-17RA) as a modulator of influenza host response and inflammation in the upper respiratory tract. We used a combined experimental approach involving IL-17RA-/- mice and an air-liquid interface (ALI) epithelial culture model to investigate the role of IL-17 response in epithelial inflammation, barrier function, and tissue pathology. Our data show that IL-17RA-/- mice exhibited significantly reduced neutrophilia, epithelial injury, and viral load. The reduced NP inflammation and epithelial injury in IL-17RA-/- mice correlated with increased resistance against co-infection by Streptococcus pneumoniae (Spn). IL-17A treatment, while potentiating the apoptosis of IAV-infected epithelial cells, caused bystander cell death and disrupted the barrier function in ALI epithelial model, supporting the in vivo findings., Competing Interests: All authors have read and approved the final version of the manuscript. The authors have declared that no conflict of interest exists., (Copyright: © 2023 Navaeiseddighi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Emerging research demonstrates that social isolation and loneliness are linked to significant physical and mental health conditions. To address these concerns, the Tellegacy program was developed as an intergenerational health-promoting intervention to ameliorate older adult social isolation and loneliness in an effort to increase wellness. The purpose of this study was to reflect on testing of the Tellegacy program as a behavioral intervention. University students trained in goal setting, mindfulness, and listening strategies were paired with 11 older adults in the northern Midwest area via weekly in-person and phone conversations. Oral reminiscence therapies were used and books containing their stories were given to the older adults after participation. Older adults were surveyed using the University of California Los Angeles Loneliness Scale, Satisfaction of Life Scale, and patient health questionnaire-9 (PHQ-9) scale to elucidate the effectiveness of the intervention. Improved scores in loneliness, satisfaction of life, and PHQ-9 demonstrated favorable improvements in older adults. Additional benefits for the student Legacy Builder were revealed from self-reported changes. This suggests the potential benefits of structured encounters between trained students and isolated or lonely older adults. The Tellegacy intergenerational feasibility program warrants further studies to fully demonstrate its impact on health outcomes.

Background: Instrumental activities of daily living (IADL) are neuropsychological-driven tasks that are linked to cognitive dysfunction. Examining population-based IADL deficits may reveal insights for the presence of these impairments in the United States., Objective: This investigation sought to evaluate the prevalence and trends of IADL impairments in Americans., Methods: A secondary analysis of data from the 2006-2018 waves of the Health and Retirement Study was conducted. The overall unweighted analytic sample included 29,764 Americans aged≥50 years. Respondents indicated their ability to perform six IADLs: manage money, manage medications, use a telephone, prepare hot meals, shop for groceries, and use a map. Persons reporting difficulty or an inability to complete an individual IADL were considered as having a task-specific impairment. Similarly, those indicating difficulty or an inability to perform any IADL were classified as having an IADL impairment. Sample weights were utilized to generate nationally-representative estimates., Results: Having an impairment in using a map (2018 wave: 15.7% (95% confidence interval (CI): 15.0-16.4) had the highest prevalence in individual IADLs regardless of wave examined. The overall prevalence of IADL impairments declined during the study period ( p  < 0.001) to 25.4% (CI: 24.5-26.2) in the 2018 wave. Older Americans and women had a consistently higher prevalence of IADL impairments compared to middle-aged Americans and men, respectively. The prevalence of IADL impairments was also highest among Hispanics and non-Hispanic Blacks., Conclusion: IADL impairments have declined over time. Continued surveillance of IADLs may help inform cognitive screening, identify subpopulations at risk of impairment, and guide relevant policy., Competing Interests: The authors have no conflict of interest to report., (© 2023 – The authors. Published by IOS Press.)

Background: We sought to examine the associations of pulse pressure (PP) and mean arterial pressure (MAP) on physical function in older Americans., Methods: Our analytic sample included 10,478 adults aged ≥65 years from the 2006-2016 Health and Retirement Study. Handgrip strength, gait speed, and standing balance were collected using relatively standard protocols. PP and MAP were calculated from blood pressure measurements., Results: Older Americans with any abnormality in PP had 1.15 (95% confidence interval (CI): 1.05-1.25) greater odds for slowness and 1.14 (CI: 1.05-1.24) greater odds for poorer standing balance. Persons with any abnormality in MAP had 0.90 (CI: 0.82-0.98) decreased odds for weakness and 1.10 (CI: 1.01-1.20) greater odds for poorer standing balance. Those with low PP had 1.19 (CI: 1.03-1.36) greater odds for slow gait speed, while persons with low MAP had 1.50 (CI: 1.09-2.05) greater odds for weakness and 1.45 (CI: 1.03-2.04) greater odds for slowness. Older Americans with high PP had 1.13 (CI: 1.03-1.25) greater odds for slowness and 1.21 (CI: 1.10-1.32) greater odds for poorer balance, whereas those with high MAP had 0.87 (CI: 0.80-0.95) decreased odds for weakness., Conclusions: Cardiovascular dysfunction, as observed by PP and MAP, may help to explain some of our findings.

Senior population health often is underrepresented in curricula for medical and allied health students. Furthermore, entrenched and dense curricular schedules preclude interprofessional teams from clinical experiences related to senior population health. Community service learning potentially offers the opportunity to engage interprofessional students with a panel of older adults to assess health promotion metrics over time. To test this educational concept, we created Health Ambassador Teams for Seniors, also known as HATS. Utilizing a telehealth platform, interprofessional student teams were tasked with older adult wellness promotion. The annual Medicare wellness exam served as a template for patient encounters which was enhanced with key elements of geriatric assessment such as gait and balance, cognition, and functional evaluations. The objective was to have dyads of interprofessional students conduct telehealth visits and gather healthcare data to be used for serial patient encounters and track functional trajectories over time. As a proof of concept, pilot telehealth encounters with medical, physical therapy, nursing and occupational therapy students revealed that data on older adult functional performances such as gait speed, Timed Up and Go test (TUG), and Mini-Cog test could be acquired through telehealth. Equally importantly, trainees received diverse feedback from faculty, peers and volunteer patients. A Research Electronic Data Capture (REDCap) data repository allows trainees to track patient trends relative to their health promotion recommendations as well as handoff their patient panel to the next set of trainees. The HATS program promises to strengthen the Geriatric Workforce, especially with senior population health.

Competing Interests: No conflicts of interest.

Background: Emergency Departments (EDs) are common entry points to the health care system for elders. Emergency Medicine residents need specialized education about geriatric patients to maximize health outcomes., Objectives: To determine whether geriatric education provided to residents in Emergency Medicine results in improved knowledge of and attitudes toward geriatric patients., Method: A pre- and post-intervention survey was conducted in a 3-year university-based residency program in Emergency Medicine. Participants were Emergency Medicine residents (PGY 1-3). The curriculum "Care of the Aging Patient in Emergency Medicine" was introduced. Topic selection was based upon geriatric curriculum recommendations and resident surveys. Before starting the curriculum and at its conclusion, residents completed Geriatric Clinical Decision-making Assessments and the Geriatric Attitude Scale Survey. Pre- and post-assessments were compared. Residents also completed written assessments for each educational activity in the curriculum., Results: After participating in the program, residents demonstrated improved knowledge of the geriatric patient, and their attitudes toward caring for geriatric patients had shifted from negative to neutral or positive. One statistically relevant change centered on the item, "Taking a medical history from an elderly patient is an ordeal" (p = 0.033) Pre-intervention, 8.3% (n = 3) of residents strongly agreed with the statement. After the intervention, strong disagreement with the statement increased from 2.8% (n = 1) to 11% (n = 4) on the educational surveys. In addition, an increase in the percentage of neutral responses was observed., Conclusions: Using familiar educational formats with heavy emphasis on "hands-on" activities to present the geriatric care curriculum had a positive impact on resident knowledge and confidence in dealing with geriatric patients., (Published by Elsevier Inc.)

Hormesis may result when mild repetitive stress increases cellular defense against diverse injuries. This process may also extend in vitro cellular proliferative life span as well as delay and reverse some of the age-dependent changes in both replicative and non-replicative cells. This study evaluated the potential hormetic effect of non-thermal repetitive electromagnetic field shock (REMFS) and its impact on cellular aging and mortality in primary human T lymphocytes and fibroblast cell lines. Unlike previous reports employing electromagnetic radiation, this study used a long wave length, low energy, and non-thermal REMFS (50MHz/0.5W) for various therapeutic regimens. The primary outcomes examined were age-dependent morphological changes in cells over time, cellular death prevention, and stimulation of the heat shock response. REMFS achieved several biological effects that modified the aging process. REMFS extended the total number of population doublings of mouse fibroblasts and contributed to youthful morphology of cells near their replicative lifespan. REMFS also enhanced cellular defenses of human T cells as reflected in lower cell mortality when compared to non-treated T cells. To determine the mechanism of REMFS-induced effects, analysis of the cellular heat shock response revealed Hsp90 release from the heat shock transcription factor (HSF1). Furthermore, REMFS increased HSF1 phosphorylation, enhanced HSF1-DNA binding, and improved Hsp70 expression relative to non-REMFS-treated cells. These results show that non-thermal REMFS activates an anti-aging hormetic effect as well as reduces cell mortality during lethal stress. Because the REMFS configuration employed in this study can potentially be applied to whole body therapy, prospects for translating these data into clinical interventions for Alzheimer's disease and other degenerative conditions with aging are discussed.

Background & Aims: Mesalamine has many effects and is commonly used for the treatment of inflammatory bowel diseases. Because sodium salicylate, a related compound, modulates the heat shock protein (hsp72) response in nonepithelial cells, the possibility that mesalamine confers cell protection by increasing intestinal epithelial hsp72 expression was examined., Methods: Rat intestinal IEC-18 cells were treated with 0.3-3 mmol/L mesalamine and thermally stressed (39 degrees C-42 degrees C) for 23 minutes. The effects of mesalamine on basal expression and the threshold and time course of hsp72 thermal induction were determined., Results: Although mesalamine had no effects on the basal hsp72 expression or its thermal activation threshold in IEC-18 cells, it accelerated and augmented thermal induction of hsp72 within the first 2 hours of exposure. This was associated with a transient increase in heat shock factor-heat shock element binding and enhanced cellular protection against oxidant-induced injury. In contrast, both mesalamine and sodium salicylate have been shown to lower the thermal induction threshold but not to enhance the hsp72 response in HeLa cells., Conclusions: Mesalamine augments thermal induction of the intestinal epithelial hsp72 expression in a manner that differs from that in nonintestinal epithelial cells. This effect is accompanied by increased cellular protection against oxidant injury.

Ultraviolet light (UV) induces a stress response mediated through transcription factors such as NF-kB and AP-1, yet little is known about its effect on other transactivators of stress gene expression such as heat shock factor (HSF1). Analysis of UV-treated HeLa cells unexpectedly revealed uncoupling of the heat shock response. UV weakly induced HSF1 into its DNA bound state and markedly attenuated heat-inducible gene expression. HSF1 was further analyzed as a potential target for the uncharacteristic uncoupling of the thermal stress response by another type of stress. Heat-inducible multimerization and nuclear translocation of HSF1 were found to be intact in UV-treated cells; however, the monomeric rather than the multimeric form of HSF1 become hyperphosphorylated by UV. This effect could be partially abolished by the antioxidant N-acetyl cysteine with partial reconstitution of hs gene expression. The reported role of a MAP kinase blockade of HSF1 transactivating properties could not be confirmed by an inhibitor of the MAP kinase pathway. Fibroblasts defective in SAP kinase activity also did not exhibit resistance to UV-inducible phosphorylation of HSF1. Two-dimensional phosphopeptide mapping of HSF1 revealed a single tryptic peptide to be affected by UV, but no new pattern of phosphorylation was evident relative to tryptic phosphopeptide profile observed in control cells. These data suggest that UV uncoupling of the hs response possibly involves steps in addition to those associated with phosphorylation the monomeric form of HSF1.

Sodium salicylate, an anti-inflammatory agent, was examined for its effects on the heat shock response in cultured human cells. Salicylate activation of DNA binding by the heat shock transcription factor (HSF) was comparable to activation attained during heat shock. However, sodium salicylate did not induce heat shock gene transcription even though the HSF was bound in vivo to the heat shock elements upstream of the heat shock protein 70 (Hsp 70) gene. These results reveal that activation of the heat shock transcriptional response is a multistep process. Modulation of extracellular pH augments sensitivity to salicylate-induced activation of HSF.

The regulation of S6 kinase activity was used to monitor perturbations of intracellular signaling activity during heat shock of quiescent murine and human fibroblasts. Previous reports on exponentially growing insect and plant cells had indicated that 40S ribosomal protein S6 is dephosphorylated during heat shock; thus inhibition of S6 kinase activity by heat shock was anticipated in NIH 3T3 fibroblasts and human cells (HeLa, diploid embryonic fibroblasts MRC-5, and skin-derived fibroblasts). Unexpectedly, two distinct S6 protein kinases were activated in quiescent fibroblasts after heat exposure. One of the enzymes was partially purified by sequential column chromatography and was determined to be equivalent to the enzyme activated by serum and other growth factors, referred to here as pp70-S6 protein kinase. The other protein S6 kinase, pp90rsk, was identified by a specific immunoprecipitation assay. Monitoring both enzymatic activities during heat shock revealed a temporal pattern of activation that was reversed when compared to non-stressed, mitogen-stimulated cells. Finally, heat shock stimulated protein S6 phosphorylation in cultured, quiescent mammalian cells. These data demonstrate that specific protein kinases can be activated during heat shock, and that some early mitogenic signals may also participate in the response of cells to physiologic stress.

A case reported here of Haloperidol-induced neutropenia demonstrates one of many important drug reactions to which the elderly may be predisposed. Neuroleptics can lead to neutropenia by toxic or immunologic mechanisms, and it is impossible to predict which patients will sustain this potentially life-threatening reaction. Fever and infection may be the only clue to this blood dyscrasias. The diagnosis of drug-induced neutropenia is largely one of exclusion coupled with the observation of increasing neutrophil counts after cessation of the drug.