Weakness Thresholds Are Differentially Linked to Cognitive Function by Obesity Status in Older Americans.

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/m2 (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/m2. The modified Telephone Interview of Cognitive Status examined cognitive function. Persons scoring ≤10 had a cognitive impairment. Obesity was categorized as BMI ≥30 kg/m2. 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.

A geriatric game to strengthen older adult healthcare delivery and outcomes.

BACKGROUND: Serious games enhance learner engagement and knowledge, yet few medical education games target older adults' healthcare. Addressing this gap, we developed Geri-POP (Geriatrics Population Health), focusing on the Age-Friendly Health System (AFHS) framework and Geriatric 4Ms. METHODS: Geri-POP, a healthcare game is aimed at educating health profession learners about the AFHS framework. Geri-POP employs plan-do-study-act cycles of rapid improvement to apply AFHS principles and explore evidence-based geriatric practices within the game environment while garnering points for insight, trust and outcomes. Faculty and medical students were surveyed for feedback on an alpha version of Geri-POP. RESULTS: Players manage patient panels across three age groups (65-74, 75-84, and 85 years and older) while engaging in plan-do-study-act (PDSA) cycles, applying Geriatric 4Ms (What Matters, Medications, Mentation, and Mobility), and refining strategies based on resource utilization, health outcomes, and real-time feedback. Alpha testing of the game received mixed perceptions on graphics, with faculty endorsing the game for training and integration into the curriculum, while students prioritize academic commitments. Suggestions include enhancing graphics and refining dialogue for a more professional tone. CONCLUSIONS: Geri-POP demonstrates the potential of gamifying older adult population health and quality improvement around AFHS. Feedback on a prototype game revealed different attitudes between faculty and students, thus emphasizing the importance of game development as an iterative process that accounts for educator and learner-centric needs. A future consideration is whether the game informs user's clinical practices and changes healthcare outcomes for older adults.

Collective Weakness Is Associated With Time to Mortality in Americans.

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.

Age-related dysregulation of intestinal epithelium fucosylation is linked to an increased risk of colon cancer.

Colon cancer affects people of all ages. However, its frequency, as well as the related morbidity and mortality, are high among older adults. The complex physiological changes in the aging gut substantially limit the development of cancer therapies. Here, we identify a potentially unique intestinal microenvironment that is linked with an increased risk of colon cancer in older adults. Our findings show that aging markedly influenced persistent fucosylation of the apical surfaces of intestinal epithelial cells, which resulted in a favorable environment for tumor growth. Furthermore, our findings shed light on the importance of the host-commensal interaction, which facilitates the dysregulation of fucosylation and promotes tumor growth as people get older. We analyzed colonic microbial populations at the species level to find changes associated with aging that could contribute to the development of colon cancer. Analysis of single-cell RNA-sequencing data from previous publications identified distinct epithelial cell subtypes involved in dysregulated fucosylation in older adults. Overall, our study provides compelling evidence that excessive fucosylation is associated with the development of colon cancer, that age-related changes increase vulnerability to colon cancer, and that a dysbiosis in microbial diversity and metabolic changes in the homeostasis of older mice dysregulate fucosylation levels with age.

A novel approach to quantifying individual's biological aging using Korea's national health screening program toward precision public health.

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.

Disrupted HSF1 regulation in normal and exceptional brain aging.

Brain aging is a major risk factor for cognitive diseases such as Alzheimer's disease (AD) and vascular dementia. The rate of aging and age-related pathology are modulated by stress responses and repair pathways that gradually decline with age. However, recent reports indicate that exceptional longevity sustains and may even enhance the stress response. Whether normal and exceptional aging result in either attenuated or enhanced stress responses across all organs is unknown. This question arises from our understanding that biological age differs from chronological age and evidence that the rate of aging varies between organs. Thus, stress responses may differ between organs and depend upon regenerative capacity and ability to manage damaged proteins and proteotoxicity. To answer these questions, we assessed age-dependent changes in brain stress responses with normally aged wild type and long-lived Dwarf mice. Results from this study show that normal aging unfavorably impacts activation of the brain heat shock (HS) axis with key changes noted in the transcription factor, HSF1, and its regulation. Exceptional aging appears to preserve and strengthen many elements of HSF1 activation in the brain. These results support the possibility that reconstitution of aging brain stress responses requires a multi-factorial approach that addresses HSF1 protein levels, its DNA binding, and regulatory elements such as phosphorylation and protein interactions.

IL-17RA promotes pathologic epithelial inflammation in a mouse model of upper respiratory influenza infection.

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.

Tellegacy: An Intergenerational Wellness and Health Promotion Project to Reduce Social Isolation and Loneliness in Older Adults: A Feasibility Study.

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.

Examining the role of different weakness categories for mobility and future falls in older Americans.

BACKGROUND: Recently developed absolute and body size normalized handgrip strength (HGS) cut-points could be used individually and collectively to predict mobility problems and falls. AIMS: We examined the associations of (1) each absolute and normalized weakness cut-point, (2) collective weakness categories, and (3) changes in weakness status on future falls in older Americans. METHODS: The analytic sample included 11,675 participants from the 2006-2018 waves of the Health and Retirement Study. Falls were self-reported. Men were classified as weak if their HGS was < 35.5-kg (absolute), < 0.45 kg/kg (body mass normalized), or < 1.05 kg/kg/m2 (body mass index normalized). While, women were considered weak if their HGS was < 20.0-kg, < 0.337 kg/kg, or < 0.79 kg/kg/m2. Collective weakness categorized those below 1, 2, or all 3 cut-points. The collective weakness categories were also used to observe changes in weakness status over time. RESULTS: Older Americans below each absolute and normalized cut-point had greater odds for future falls: 1.23 (95% confidence interval (CI): 1.15-1.32) for absolute weakness, 1.20 (CI 1.11-1.29) for body mass index normalized weakness, and 1.26 (CI 1.17-1.34) for body mass normalized weakness. Persons below 1, 2, or all 3 weakness cut-points had 1.17 (CI 1.07-1.27), 1.29 (CI 1.18-1.40), and 1.36 (CI 1.24-1.48) greater odds for future falls, respectively. Those in some changing weakness categories had greater odds for future falls: 1.26 (CI 1.08-1.48) for persistent and 1.31 (CI 1.11-1.55) for progressive. DISCUSSION: Collectively using these weakness cut-points may improve their predictive value. CONCLUSION: We recommend HGS be evaluated in mobility and fall risk assessments.

The Prevalence and Trends of Instrumental Activities of Daily Living Impairments in the United States from 2008-2018.

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.

The Associations of Pulse Pressure and Mean Arterial Pressure on Physical Function in Older Americans.

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.

Handgrip Strength Asymmetry Is Associated With Limitations in Individual Basic Self-Care Tasks.

This investigation sought to determine the associations between handgrip strength (HGS) asymmetries and limitations in individual activities of daily living (ADL). The analytic sample included 18,468 participants from the 2006 to 2016 waves of the Health and Retirement Study. Those with HGS >10% stronger on either hand had any HGS asymmetry. Individuals with HGS >10% stronger on their dominant or non-dominant hand had dominant or non-dominant HGS asymmetry, respectively. ADL abilities were self-reported. Those with any HGS asymmetry had 1.21 (95% confidence interval [CI] = [1.01-1.46]) greater odds for a toileting limitation and 1.25 (CI = [1.03-1.52]) greater odds for a transferring limitation. Individuals with dominant HGS asymmetry had 1.24 (CI = [1.01-1.53]) greater odds for a transferring limitation. Those with non-dominant HGS asymmetry had 1.39 (CI = [1.01-1.93]) and 1.44 (CI = [1.05-1.96]) greater odds for a bathing and toileting limitation, respectively. HGS asymmetries could help to identify future limitations in specific ADLs.

The estimated prevalence of no reported dementia-related diagnosis in older Americans living with possible dementia by healthcare utilization.

BACKGROUND: Screening for dementia in relevant healthcare settings may help in identifying low cognitive functioning for comprehensive cognitive assessments and subsequent dementia treatment after diagnosis. AIMS: This study sought to estimate the prevalence of no reported dementia-related diagnosis in a nationally-representative sample of older Americans with a cognitive impairment consistent with dementia (CICD) by healthcare utilization. METHODS: The unweighted analytical sample included 1514 Americans aged ≥ 65 years that were identified as having a CICD without history of stroke, cancers, neurological conditions, or brain damage who participated in at least one-wave of the 2010-2016 waves of the Health and Retirement Study. An adapted Telephone Interview of Cognitive Status assessed cognitive functioning. Those with scores ≤ 6 had a CICD. Dementia-related diagnosis was self-reported. Respondents indicated if they visited a physician, received home healthcare, or experienced an overnight nursing home stay in the previous two years. RESULTS: The prevalence of no reported dementia-related diagnosis in persons with a CICD who visited a physician was 89.9% (95% confidence interval (CI): 85.4%-93.1%). Likewise, the prevalence of no reported diagnosis in those with a CICD who received home healthcare was 84.3% (CI: 75.1-90.5%). For persons with a CICD that had an overnight nursing home stay, the prevalence of no reported dementia-related diagnosis was 83.0% (CI: 69.1-91.4%). DISCUSSION: Although the prevalence of no reported dementia-related diagnosis in individuals with a CICD differed across healthcare settings, the prevalence was generally high nonetheless. CONCLUSIONS: We recommend increased awareness and efforts be given to dementia screenings in various clinical settings.

Handgrip Strength Asymmetry and Weakness Are Associated With Future Morbidity Accumulation in Americans.

ABSTRACT: Klawitter, L, Vincent, BM, Choi, BJ, Smith, J, Hammer, KD, Jurivich, DA, Dahl, LJ, and McGrath, R. Handgrip strength asymmetry and weakness are associated with future morbidity accumulation in americans. J Strength Cond Res 36(1): 106-112, 2022-Identifying strength asymmetries in physically deconditioned populations may help in screening and treating persons at risk for morbidities linked to muscle dysfunction. Our investigation sought to examine the associations between handgrip strength (HGS) asymmetry and weakness on accumulating morbidities in aging Americans. The analytic sample included 18,506 Americans aged ≥50 years from the 2006-2016 Health and Retirement Study. Handgrip strength was measured on each hand with a handgrip dynamometer, and persons with an imbalance in strength >10% between hands had HGS asymmetry. Men with HGS <26 kg and women with HGS <16 kg were considered as weak. Subjects reported the presence of healthcare provider-diagnosed morbidities: hypertension, diabetes, cancer, chronic lung disease, cardiovascular disease, stroke, arthritis, and psychiatric problems. Covariate-adjusted ordinal generalized estimating equations analyzed the associations for each HGS asymmetry and weakness group on future accumulating morbidities. Of those included in our study, subjects at baseline were aged 65.0 ± 10.2 years, 9,570 (51.7%) had asymmetric HGS, and 996 (5.4%) were weak. Asymmetry alone and weakness alone were associated with 1.09 (95% confidence interval [CI]: 1.04-1.14) and 1.27 (CI: 1.11-1.45) greater odds for future accumulating morbidities, respectively. Having both HGS asymmetry and weakness was associated with 1.46 (CI: 1.29-1.65) greater odds for future accumulating morbidities. Handgrip-strength asymmetry, as another potential indicator of impaired muscle function, is associated with future morbidity status during aging. Exercise professionals and related practitioners should consider examining asymmetry and weakness with handgrip dynamometers as a simple and noninvasive screening method for helping to determine muscle dysfunction and future chronic disease risk.

A New Interprofessional Community-Service Learning Program, HATS (Health Ambassador Teams for Seniors) to Improve Older Adults Attitudes about Telehealth and Functionality.

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.

A simplified and sensitive immunoprecipitation approach for the analysis of HSF1 in murine liver tissue.

Heat shock factor 1, HSF1, is one of several family members that recognize repeated nGAAn sequences associated with the heat shock element of heat shock and other genes. This transactivator is activated from a monomeric to trimeric form by oxidative, thermal and other stressors. Various studies show that HSF1 levels increase with cancer and decrease with aging and neurodegenerative disorders. It has a role in development as well as infections and inflammation. HSF1 is regulated by post-translational modifications and interactions with other proteins such as HSBP-1. Given its central importance in stress responsivity, various methods have been developed to identify HSF1 and its interacting partners. To date, multiple studies use conventional immunoprecipitation of HSF1 with commercially available antibodies which work well in cell lines but not whole tissue extracts. To remedy this shortfall, we developed a technique to retrieve activated HSF1 with an oligonucleotide link to a magnetic bead. The method captures HSF1 using a DNA sequence specific for HSF1 binding sites on promoter of heat shock genes. Confirmation of tissue derived HSF1 is identified using antibody against HSF1. The magnetic beads conjugated with DNA sequence specific to HSF1 binding was capable of yielding a reproducible band of high signal intensity with low background after native gel electrophoresis and ECL. Thus, the trimeric form of HSF1 can be isolated from tissue with magnetic beads conjugated with a short DNA sequence specific to HSF1 binding. This new method to identify HSF1 is economic, easy, and reproducible and does not require specialized equipment. It overcomes limitations of HSF1 tissue extraction by conventional immunoprecipitation, thus allowing for new approaches to understand HSF1 function in animal and human tissue.•HSF1 is a transcription factor that homotrimerize and binds to a conserved regulatory site, the heat shock element (HSE), consists of repeats of pentameric sequence '5-nGAAn-3' present in the promoters of inducible heat shock protein genes.•This protocol allows isolation of trimeric forms of HSF1 from tissue lysate using magnetic beads conjugated with a short DNA sequence with specific binding to HSF1.•This method is easy, economic and does not require unique instrumentation.

Assessing Additional Characteristics of Muscle Function With Digital Handgrip Dynamometry and Accelerometry: Framework for a Novel Handgrip Strength Protocol.

Maximal handgrip strength (HGS) is a convenient and reliable, but incomplete, assessment of muscle function. Although low HGS is a powerful predictor of poor health, several limitations to maximal HGS exist. The predictive value of HGS is restricted because low HGS is associated with a wide range of unspecified health conditions, and other characteristics of muscle function aside from strength capacity are not evaluated. Current HGS protocol guidelines emphasize the ascertainment of maximal force, which is only a single muscle function characteristic. Muscle function is intrinsically multivariable, and assessing other attributes in addition to strength capacity will improve screenings for age-related disabilities and diseases. Digital handgrip dynamometers and accelerometers provide unique opportunities to examine several aspects of muscle function beyond strength capacity, while also maintaining procedural ease. Specifically, digital handgrip dynamometry and accelerometry can assess the rate of force development, submaximal force steadiness, fatigability, and task-specific tremoring. Moreover, HGS protocols can be easily refined to include an examination of strength asymmetry and bilateral strength. Therefore, evaluating muscle function with new HGS technologies and protocols may provide a more comprehensive assessment of muscle function beyond maximal strength, without sacrificing feasibility. This Special Article introduces a novel framework for assessing multiple attributes of muscle function with digital handgrip dynamometry, accelerometry, and refinements to current HGS protocols. Such framework may aid in the discovery of measures that better predict and explain age-related disability, biological aging, and the effects of comorbid diseases that are amenable to interventions. These additional HGS measures may also contribute to our understanding of concepts such as resilience. Using sophisticated HGS technologies that are currently available and modernizing protocols for developing a new muscle function assessment may help transform clinical practice by enhancing screenings that will better identify the onset and progression of the disabling process.

Augmentation of the heat shock axis during exceptional longevity in Ames dwarf mice.

How the heat shock axis, repair pathways, and proteostasis impact the rate of aging is not fully understood. Recent reports indicate that normal aging leads to a 50% change in several regulatory elements of the heat shock axis. Most notably is the age-dependent enhancement of inhibitory signals associated with accumulated heat shock proteins and hyper-acetylation associated with marked attenuation of heat shock factor 1 (HSF1)-DNA binding activity. Because exceptional longevity is associated with increased resistance to stress, this study evaluated regulatory check points of the heat shock axis in liver extracts from 12 months and 24 months long-lived Ames dwarf mice and compared these findings with aging wild-type mice. This analysis showed that 12M dwarf and wild-type mice have comparable stress responses, whereas old dwarf mice, unlike old wild-type mice, preserve and enhance activating elements of the heat shock axis. Old dwarf mice thwart negative regulation of the heat shock axis typically observed in usual aging such as noted in HSF1 phosphorylation at Ser307 residue, acetylation within its DNA binding domain, and reduction in proteins that attenuate HSF1-DNA binding. Unlike usual aging, dwarf HSF1 protein and mRNA levels increase with age and further enhance by stress. Together these observations suggest that exceptional longevity is associated with compensatory and enhanced HSF1 regulation as an adaptation to age-dependent forces that otherwise downregulate the heat shock axis.

Handgrip Strength Asymmetry and Weakness Together Are Associated With Functional Disability in Aging Americans.

BACKGROUND: Evaluating handgrip strength (HGS) asymmetry may help to improve the prognostic value of HGS. This study sought to determine the associations of HGS asymmetry and weakness on future activities of daily living (ADL) disability in a national sample of aging Americans. METHODS: The analytic sample included 18,468 Americans aged ≥50 years from the 2006-2016 waves of the Health and Retirement Study. A handgrip dynamometer measured HGS. Those with HGS >10% stronger on either hand were considered as having any HGS asymmetry. Individuals with HGS >10% stronger on their dominant hand were considered as having dominant HGS asymmetry, while those with HGS >10% stronger on their nondominant hand were classified as having nondominant HGS asymmetry. Men with HGS <26 kg and women with HGS <16 kg were considered weak. ADLs were self-reported. Generalized estimating equations were used for analyses. RESULTS: Relative to those with symmetric HGS and no weakness, each HGS asymmetry and weakness group had increased odds for future ADL disability: 1.11 (95% confidence interval [CI]: 1.02-1.20) for any HGS asymmetry alone, 1.42 (CI: 1.16-1.74) for weakness alone, and 1.81 (CI: 1.52-2.16) for both any HGS asymmetry and weakness. Most weakness and HGS asymmetry dominance groups had increased odds for future ADL disability: 1.30 (CI: 1.13-1.50) for nondominant HGS asymmetry alone, 1.42 (CI: 1.16-1.74) for weakness alone, 1.72 (CI: 1.29-2.29) for both weakness and nondominant HGS asymmetry, and 1.86 (CI: 1.52-2.28) for both weakness and dominant HGS asymmetry. CONCLUSIONS: HGS asymmetry and weakness together may increase the predictive utility of handgrip dynamometers.