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Background Chronic pain has been associated with accelerated biological aging, which may be related to epigenetic alterations. We evaluated the association of high-impact pain (ie, pain that limits activities and function) with epigenetic aging, a measure of biological aging, in a nationally representative sample of middle-aged and older adults in the United States. Methods Cross-sectional analysis of adults 50 years of age and older from the 2016 Health and Retirement Study. Epigenetic aging was derived from 13 epigenetic clocks based on DNA methylation patterns that predict aging correlates of morbidity and mortality. Ordinary least squares regressions were performed to test for differences in the epigenetic clocks, adjusting for the complex survey design, as well as biological, social, and behavioral factors. Results The analysis consisted of 3 855 adults with mean age of 68.5 years, including 59.8% with no pain and 25.8% with high-impact pain. Consistent with its operational definition, high-impact pain was associated with greater functional and activity limitations. High-impact pain was associated with accelerated epigenetic aging compared to no pain, as measured via second (Zhang, PhenoAge, GrimAge) and third (DunedinPoAm) generation epigenetic clocks. Additionally, GrimAge was accelerated in high-impact pain as compared to low-impact pain. Conclusions High-impact pain is associated with accelerated epigenetic aging among middle-aged and older adults in the United States. These findings highlight aging-associated epigenetic alterations in high-impact chronic pain and suggest a potential for epigenetic therapeutic approaches for pain management and the preservation of physical function in older adults. [ABSTRACT FROM AUTHOR]

Background Frailty is associated with urinary and fecal incontinence, which are common geriatric syndromes. This study aims to identify health factors associated with incontinence in prefrail or frail older adults living in the community. Methods This multicenter cross-sectional study included 225 older adults (75.0 ± 6.4 years) with prefrailty or frailty based on the 5-component Fried phenotype. Physical function was assessed using the Short Physical Performance Battery (SPPB). Physical activity, inactivity, and sleep were estimated using a wrist-worn accelerometer. Urinary or fecal incontinence was registered using the Barthel scale (urine and bowel items). Multivariable logistic regression analyses, with age as a covariate, were conducted to identify associations of incontinence. Results In our participants, 27% presented urinary or fecal incontinence with no sex differences (p  = .266). Our results showed that age, daily medication count, and number of falls in the previous year independently predicted incontinence in frail and prefrail older adults (p  < .05). Some Fried's criteria, including self-reported exhaustion, gait speed, and handgrip strength, were associated with the presence of incontinence (p  < .05), but not Fried's classification. The SPPB total score and its isolated variables were significantly associated with the urinary and fecal incontinence (p  < .05). However, none of the accelerometer outcomes showed significant associations with incontinence status. Conclusions According to this study, age, number of medications, and falls (but not sex) are linked to urinary and fecal incontinence in frail or prefrail older adults living in the community, recommending the assessment of physical function using the SPPB rather than estimating daily physical activity, inactivity, or sleep. [ABSTRACT FROM AUTHOR]

Background This study examined the relation between declines in physical and cognitive performance in older people. Methods A population-based cohort of 7 483 adults (average age 72 years) were interviewed. Physical performance was assessed with 3 standardized tests and a combination of 4 cognitive tests was used to assess cognitive function. Rate of change in physical and cognitive performance was determined for each interval between interviews. In mixed effects linear regression models adjusted for age, sex, race, and study time, and change in each factor was used to predict change in the other factor. We examined time associations by using changes in the predictor measured at 1, 2, or 3 intervals before the outcome change. Results Decline in cognitive function was most strongly predicted by physical decline in the same 3-year interval. The decline in cognitive function was weaker in the 1-time interval after the decline in physical function and was not significant in later intervals. When a decline in cognitive function was used to predict a decline in physical function, the results were similar. The strongest association occurred in the same time interval so that declines in cognitive and physical performance tend to occur together. Conclusions Decline in cognition and physical function seem to occur together in a short timeframe. It is important to investigate the reasons for these changes that are short-term to guide the development of interventions. [ABSTRACT FROM AUTHOR]

Background Older adults reporting higher energy levels have better physical function. It is not known if these associations persist among older adults reporting fatigue or if higher energy is associated with cognitive function. We examined longitudinal associations between self-reported energy, gait speed, and cognition, stratified by fatigue, in 2 613 participants (aged 74.6 ± 2.87 years) in the Health, Aging and Body Composition Study. Methods Self-reported energy (0–10, dichotomized at median) and fatigue (present/absent) were measured at baseline. Usual and rapid-paced gait speed (m/s), modified Mini-Mental State Examination (3MS), and Digit Symbol Substitution Test (DSST) were measured at baseline and annually over 8 years. Linear mixed effect models compared changes in gait speed, 3MS, and DSST between higher and lower energy groups within fatigue strata. Results At baseline, 724 participants (27%) were fatigued; 240 (33%) coreported higher energy (9% of total). The remaining 1 889 participants were fatigue-free (73%); 1 221 (65%) coreported higher energy (47% of total). Those with fatigue and higher energy had average rapid gait declines of 0.007 m/s per year (p  = .04) after adjustment for demographics, comorbidities, depressive symptoms, and exercise. DSST declines were found among only fatigue-free participants (β = 0.17, p  = .01). No statistically significant associations with energy were found for fatigue-free participants, or for usual gait or 3MS. Conclusions Asking about older adults' energy levels as well as fatigue may identify a subgroup of older adults protected against physical and cognitive decline, even among those with fatigue. [ABSTRACT FROM AUTHOR]

Background Older adults with discordant biological and chronological ages (BA and CA) may vary in cognitive and physical function from those with concordant BA and CA. Methods To make our approach clinically accessible, we created easy-to-interpret participant groups in the Health, Aging, and Body Composition Study (N  = 2 458, 52% female participants, 65% White participants, age: 73.5 ± 2.8) based on medians of CA, and a previously validated BA index comprised of readily available clinical tests. Joint models estimated associations of BA–CA group with cognition (Modified Mini-Mental State Examination [3MS] and Digit Symbol Substitution Test [DSST]) and frailty over 10 years. Results The sample included the following: 32%, Young group (BA and CA < median); 21%, Prematurely Aging group (BA ≥ median, CA < median), 27%, Old group (BA and CA ≥ median), and 20%, Resilient group (BA < median, CA ≥ median). In education-adjusted models of cognition, among those with CA < median, the Prematurely Aging group performed worse than the Young at baseline (3MS and DSST p  < .0001), but among those with CA ≥ median, the Resilient group did not outperform the Old group (3MS p  = .31; DSST p  = .25). For frailty, the Prematurely Aging group performed worse than the Young group at baseline (p  = .0001), and the Resilient group outperformed the Old group (p  = .003). For all outcomes, groups did not differ on change over time based on the same pairwise comparisons (p  ≥ .40). Conclusions Discordant BA and CA identify groups who have greater cognitive and physical functional decline or are more protected than their CA would suggest. This information can be used for risk stratification. [ABSTRACT FROM AUTHOR]

Background Based on studies from animal models, growth differentiation factor-11 (GDF-11) may have rejuvenating effects in humans. GDF-11 has high sequence homology with GDF-8 (also known as myostatin); follistatin and follistatin-like protein-3 (FSTL-3) are inhibitory proteins of both GDF-8 and GDF-11. Methods Using highly specific liquid chromatography with tandem mass spectrometry assays for GDF-11 and GDF-8 and immunoassays for follistatin and FSTL-3, we quantified the association of these factors with muscle size, strength, and physical performance in 2 prospective cohort studies of community-dwelling older adults (Health, Aging, and Body Composition study [Health ABC] and Cardiovascular Health Study [CHS]). Results GDF-8 levels were positively associated with thigh muscle cross-sectional area and density in Health ABC (data not available in CHS). GDF-8 levels were positively associated with lean mass (a surrogate of muscle mass) in Health ABC but not CHS, and grip strength in CHS but not Health ABC. FSTL-3 (and perhaps follistatin) was negatively associated with lean mass and had variable associations with other variables. In contrast, GDF-11 was not significantly associated with strength or performance. Conclusions GDF-8 and its binding proteins, follistatin and FSTL-3, may constitute a counterregulatory system (chalones) to restrain age-related loss of muscle mass and strength. [ABSTRACT FROM AUTHOR]

Background: Multisystem dysregulation (Dm) shows promise as a metric of aging and predicts mortality. However, Dm needs to be studied with less severe endpoints indicating modifiable aging stages. Physical function, reflecting healthy longevity rather than just longevity, is more relevant to the goals of geroscience but has not been well investigated.Methods: We tested the association of midlife Dm and its change over ~20 years with physical function in later life in 5,583 ARIC cohort participants (baseline mean age 54.7). Dm quantifies the multivariate statistical deviation of 17 physiologically motivated biomarkers relative to their distribution in a young healthy sample at baseline. Physical function was assessed from grip strength and the Short Physical Performance Battery (SPPB). Associations were quantified using linear regression and ordinal logistic regression adjusting for age, sex, race, and education.Results: Each unit increment in midlife Dm was associated with 1.71 times the odds of having a lower SPPB score. Compared to the 1 st quartile of midlife Dm, the odds ratios of having a lower SPPB score were 1.25, 1.56, and 2.45, respectively, for the 2 nd-4 th quartiles. Similar graded association patterns were observed for each SPPB component test and grip strength. An inverse monotonic relationship also was observed between annual growth rate of Dm and physical function.Conclusions: Greater multisystem dysregulation and progression in midlife were associated with lower physical function in later life. Future studies on the factors that lead to progression of multisystem dysregulation may highlight opportunities to preserve physical function. [ABSTRACT FROM AUTHOR]

Background To evaluate whether contrast sensitivity is associated with lower extremity physical function in cognitively intact older adults. Methods Cross-sectional analysis of the relationship of binocular and worse eye log contrast sensitivity (LCS) to expanded Short Physical Performance Battery (eSPPB) and its components (gait speed, narrow walking speed, chair stand pace, and balance) in 192 cognitively healthy older adults. The association of LCS with postural sway and gait was also tested with tasks that further challenged functional reserve. Results Mean age was 76.4 years with 56% identifying as female and over 98.5% having good corrected visual acuity. Lower LCS was significantly associated with worse performance on the eSPPB, 4-M gait speed, narrow walking speed, and balance time in unadjusted and adjusted models. The relationship between worse eye LCS and larger postural sway was 3 times greater on a foam surface (beta 1.07, 95% CI [0.35, 1.80]) than a firm surface (beta 0.35, 95% CI [0.05, 0.65]), and both were robust to adjustment for confounders; similar findings were observed with binocular LCS. Lower binocular LCS had a greater decremental effect on gait velocity during the fast pace (beta −0.58, 95% CI [−0.90, −0.27]) than the usual pace (Beta −0.39 [−0.63, −0.15]) gait task. Conclusions These findings suggest that cognitively unimpaired older adults without significant visual acuity impairment can have subtle preclinical deficits in contrast sensitivity and physical function that could place them at risk of mobility and balance issues. Future studies should determine whether this subset of older adults may benefit from targeted intervention to prevent disability. [ABSTRACT FROM AUTHOR]

Background: A systematic review and network meta-analysis was undertaken to examine the effectiveness of different modes of resistance exercise velocity in fast walking speed, timed-up and go, five-times sit-to-stand, 30-sec sit-to-stand and 6-min walking tests in older adults.Methods: CINAHL, Embase, LILACS, PubMed, Scielo, SPORTDiscus and Web of Science databases were searched up to February 2022. Eligible randomised trials examined the effects of supervised high-velocity or traditional resistance exercise in older adults (i.e., ≥ 60 years). The primary outcome for this review was physical function measured by fast walking speed, timed up and go, five times sit-to-stand, 30-sec sit-to-stand and 6-minute walking tests, while maximal muscle power and muscle strength were secondary. A random-effects network meta-analysis was undertaken to examine the effects of different resistance exercise interventions.Results: Eighty articles describing 79 trials (n= 3,575) were included. High-velocity resistance exercise was the most effective for improving fast walking speed [standardised mean difference (SMD) -0.44, 95% CI: 0.00 to 0.87], timed-up and go (SMD -0.76, 95% CI: -1.05 to -0.47) and five times sit-to-stand (SMD -0.74, 95% CI: -1.20 to -0.27), while traditional resistance exercise was the most effective for 30-sec sit-to-stand (SMD 1.01, 95% CI: 0.68 to 1.34) and 6-min walking (SMD 0.68, 95% CI: 0.34 to 1.03).Conclusion: Our study provides evidence that resistance exercise velocity effects are specific in older adults as evidenced by physical function test dependence. We suggest that prescription based on the velocity of contraction should be individualised to address specific functional needs of participants. [ABSTRACT FROM AUTHOR]

Background This study develops a new concept, dual functionality, that integrates physical and cognitive function. We use the concept to define a measure of dual-function life expectancy (2FLE) and assess racial–ethnic inequalities in aging. Methods Drawing on data from the National Health Interview Survey Linked Mortality Files and the Health and Retirement Study, we define dual functionality as having no limitations in activities of daily living and being free of dementia. We use this measure and Sullivan life tables to estimate age-50 total life expectancy and age-50 2FLE for women and men across 4 racial–ethnic and nativity groups. Results At ages 50–54, between 79.0% (95% CI: 73.5, 84.5) and 87.6% (95% CI: 84.0, 91.2) of (non-Hispanic) Black, foreign-born Hispanic, and U.S.-born Hispanic women and men remain dual functional as compared with 90.4% (95% CI: 89.3, 91.4) and 91.4% (95% CI: 90.2, 92.5) of (non-Hispanic) White women and men, respectively. These and corresponding racial–ethnic disparities in dual functionality through ages 85 and older translate into substantial inequalities in 2FLE. For instance, the Black–White gap in age-50 2FLE is 6.9 years (95% CI: −7.5, −6.4) for women and 6.0 years (95% CI: −6.6, −5.4) for men. Conclusions Black, foreign-born Hispanic, and U.S.-born Hispanic older adults are estimated to live a smaller percentage of their remaining years with dual functionality than White older adults. These results reveal stark racial–ethnic inequalities in aging that have significant implications for quality of life, caregiving, and health needs. [ABSTRACT FROM AUTHOR]

In recent years, several new classes of therapies have been investigated with their potential for restoring or improving physical functioning in older adults. These have included Mas receptor agonists, regulators of mitophagy, skeletal muscle troponin activators, anti-inflammatory compounds, and targets of orphan nuclear receptors. The present article summarizes recent developments of the function-promoting effects of these exciting new compounds and shares relevant preclinical and clinical data related to their safety and efficacy. The development of novel compounds in this area is expanding and likely will need the advent of a new treatment paradigm for age-associated mobility loss and disability. [ABSTRACT FROM AUTHOR]

Physical activity and exercise training exert multiple and varied beneficial effects on a wide array of human tissues, making them therapeutic modalities that can prevent and treat age-related decline in physical function. The Molecular Transducers of Physical Activity Consortium is currently working to elucidate the molecular mechanisms underlying how physical activity improves and preserves health. Exercise training, especially when task specific, is an effective intervention for improving skeletal muscle performance and physical function in everyday activities. As seen elsewhere in this supplement, its adjunctive use with pro-myogenic pharmaceuticals may prove to be synergistic in effect. Behavioral strategies aiming to promote exercise participation and sustain adherence are being considered as additional adjuncts to further improve physical function in comprehensive, multicomponent interventions. One application of this combined strategy may be to target multimodal pro-myogenic therapies in prehabilitation to optimize physical preoperative health to enhance functional recovery postsurgery. We summarize here recent progress on biological mechanisms of exercise training, behavioral approaches to exercise participation, and the role task-specific exercise plays in synergy with pharmacologic therapies with a particular focus on older adults. Physical activity and exercise training in multiple settings should serve as the baseline standard of care around which other therapeutic interventions should be considered when the goal is restoring or increasing physical function. [ABSTRACT FROM AUTHOR]

Background Computed tomography (CT)-scan measures of muscle composition may be associated with recovery post hip fracture. Methods In an ancillary study to Baltimore Hip Studies Seventh cohort, older adults were evaluated at 2 and 6 months post hip fracture. CT-scan measures of muscle were acquired at 2 months. Short Physical Performance Battery (SPPB) was measured at 2 and 6 months. Generalized estimating equations were used to model the association of muscle measures and physical function, adjusting for age, sex, body mass index, and time postfracture. Results Seventy-one older adults (52% males, age 79.6 ± 7.3 years) were included. At 2-months, males had greater thigh cross-sectional area (CSA, p <.0001) and less low-density muscle (p =.047), and intermuscular adipose tissue (p =.007) than females on the side of the fracture, while females performed better on the SPPB (p =.05). Muscle measures on the fractured side were associated with function at 2 months in both sexes. Participants with the lowest tertile of muscle CSA difference at 2-months, indicating greater symmetry in CSA between limbs, performed better than the other 2 tertiles at 6-months. Males performed worse in functional measures at baseline and did not recover as well as females (p =.02). Conclusion CT-scan measures of muscle CSA and fatty infiltration were associated with function at 2-months post hip fracture and with improvement in function by 6 months. Observed sex differences in these associations suggest that rehabilitation strategies may need to be adapted by sex after hip fracture. [ABSTRACT FROM AUTHOR]

Background: A systematic review and meta-analysis was performed to evaluate the short- and long-term effects of exercise therapy on physical function, independence, and well-being in older patients following hip fracture and, secondly, whether the effect was modified by trial-level characteristics such as intervention modality, duration, and initiation timepoint.Method: Medline, CENTRAL, Embase, CINAHL, and PEDro were searched up to November 2020. Eligibility criteria were randomized controlled trials investigating the effect of exercise therapy on physical function, independence, and well-being in older patients following hip fracture, initiated from time of surgery up to 1 year.Results: Forty-nine studies involving 3 905 participants showed a small-to-moderate effect of exercise therapy at short term (end of intervention) on mobility (standardized mean difference [SMD] 0.49, 95% confidence interval [CI]: 0.22-0.76); activities of daily living (ADL) (SMD 0.31, 95% CI: 0.16-0.46); lower limb muscle strength (SMD 0.36, 95% CI: 0.13-0.60); and balance (SMD 0.34, 95% CI: 0.14-0.54). At long term (closest to 1 year), small-to-moderate effects were found for mobility (SMD 0.74, 95% CI: 0.15-1.34), ADL (SMD 0.42, 95% CI: 0.23-0.61), balance (SMD 0.50, 95% CI: 0.07-0.94), and health-related quality of life (SMD 0.31, 95% CI: 0.03-0.59). Certainty of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation ranging from moderate to very low, due to study limitation and inconsistency.Conclusion: We found low certainty of evidence for a moderate effect of exercise therapy on mobility in older patients following hip fracture at end of treatment and follow-up. Further, low evidence was found for small-to-moderate short-term effect on ADL, lower limb muscle strength and balance.Clinical Trials Registration Number: CRD42020161131. [ABSTRACT FROM AUTHOR]

Background: Delirium is common, distressing, and associated with poor outcomes. Despite this, delirium remains poorly recognized, resulting in worse outcomes. There is an urgent need for methods to objectively assess for delirium. Physical function has been proposed as a potential surrogate marker, but few studies have monitored physical function in the context of delirium. We examined if trajectories of physical function are affected by the presence and severity of delirium in a representative sample of hospitalized participants older than 65 years.Method: During hospital admissions in 2016, we assessed participants from the Delirium and Cognitive Impact in Dementia study daily for delirium and physical function, using the Hierarchical Assessment of Balance and Mobility (HABAM). We used linear mixed models to assess the effect of delirium and delirium severity during admission on HABAM trajectory.Results: Of 178 participants, 58 experienced delirium during admission. Median HABAM scores in those with delirium were significantly higher (indicating worse mobility) than those without delirium. Modeling HABAM trajectories, HABAM scores at first assessment were worse in those with delirium than those without, by 0.76 (95% CI: 0.49-1.04) points. Participants with severe delirium experienced a much greater perturbance in their physical function, with an even lower value at first assessment and slower subsequent improvement.Conclusions: Physical function was worse in those with delirium compared to without. This supports the assertion that motor disturbances are a core feature of delirium and monitoring physical function, using a tool such as the HABAM, may have clinical utility as a surrogate marker for delirium and its resolution. [ABSTRACT FROM AUTHOR]

Background: Among older adults, walking performance is a reliable indicator of adverse health outcomes including incident mobility impairment. Whereas, attention and executive functions have been implicated in cognitive control of locomotion, much less is known about the role of cognitive reserve (CR) in predicting mobility impairments among older adults. Specifically, whether CR moderates the relationship between gait performance and incident mobility impairment has not been reported. To address this gap in the literature, we examined whether gait performance under single-task walk (STW) and dual-task walk (DTW) conditions predicted incident mobility impairment and whether CR moderated this relationship.Method: Participants were 176 (mean age = 75.57; % female = 53) older adults with baseline Short Physical Performance Battery (SPPB) scores of 10-12. Participants completed neuropsychological testing, the SPPB, and a DTW protocol. CR was evaluated using the Wide Range Achievement Test, third edition. Participants were followed for 3 years; individuals whose SPPB scores declined below 10 were defined as incident cases of mobility impairment (n = 42).Results: Moderation analyses revealed significant interaction effects of CR with walking velocity under STW (b = 0.09, 95% CI [0.01, 0.17], z = 2.30, p = .02) and DTW (b = 0.10, 95% CI [0.02, 0.17], z = 2.55, p = .01) conditions, wherein slower gait predicted increased risk of incident mobility impairment among individuals with lower CR.Conclusion: These findings extend knowledge about the interrelation of cognitive and mobility functions, revealing the critical role of CR in identifying older adults at risk of developing incident mobility impairment. [ABSTRACT FROM AUTHOR]

Background: Although hearing impairment (HI) is linked to poorer physical functioning, the longitudinal associations between HI and higher-level functional measures are unclear.Method: Data are from the Baltimore Longitudinal Study of Aging (2012-2019). Using pure-tone audiometry, we categorized hearing into normal, mild, and moderate or greater HI. Physical function was assessed with the expanded Short Physical Performance Battery (eSPPB) and walking endurance with time to walk 400 m. Multivariable and mixed-effects linear models tested the hypotheses that participants with HI, at baseline, have poorer physical performance and walking endurance, and faster decline over time (up to 6 measurements). In a subset (n = 526), we further adjusted for vestibular function. Among participants with HI, we evaluated the differences in eSPPB scores and walking endurance between hearing aid users and nonusers.Results: Of 831 participants, 26% had mild, and 17% moderate or greater HI. After adjustment for demographics and medical history, moderate or greater impairment versus normal hearing was associated with poorer function (0.17 [95% CI: 0.09, 0.26] lower eSPPB score, and 13.3 [95% CI: 3.31, 23.4] seconds slower 400-m walk time) and faster decline in these parameters over 6 years. Adjustment for vestibular function did not attenuate these associations. Hearing aid users walked 400 m 24 seconds faster than nonusers (p = .001).Conclusion: Moderate or greater HI is associated with poorer initial and greater decline in higher-level physical performance. The observation that hearing aid users had better walking endurance suggests that screening for and treatment of HI may delay or slow progression of hearing-related functional decline. [ABSTRACT FROM AUTHOR]