Social isolation and loneliness as risk factors for the progression of frailty

Background: loneliness and social isolation have been associated with mortality and with functional decline in older people. We investigated whether loneliness or social isolation are associated with progression of frailty. Methods: participants were 2817 people aged ≥60 from the English Longitudinal Study of Ageing. Loneliness was assessed at Wave 2 using the Revised UCLA scale (short version). A social isolation score at Wave 2 was derived from data on living alone, frequency of contact with friends, family and children, and participation in social organizations. Frailty was assessed by the Fried phenotype of physical frailty at Waves 2 and 4, and by a frailty index at Waves 2-5. Results: high levels of loneliness were associated with an increased risk of becoming physically frail or pre-frail around 4 years later: relative risk ratios (95% CI), adjusted for age, sex, level of frailty and other potential confounding factors at baseline were 1.74 (1.29, 2.34) for pre-frailty, and 1.85 (1.14, 2.99) for frailty. High levels of loneliness were not associated with change in the frailty index—a broadly-based measure of general condition--over a mean period of 6 years. In the sample as a whole, there was no association between social isolation and risk of becoming physically frail or pre-frail, but high social isolation was associated with increased risk of becoming physically frail in men. Social isolation was not associated with change in the frailty index. Conclusions: older people who experience high levels of loneliness are at increased risk of becoming physically frail

Correlates of level and loss of grip strength in later life:Findings from the English Longitudinal Study of Ageing and the Hertfordshire Cohort Study

Characterisation of grip strength (GS) using isometric dynamometry is central to the definition of sarcopenia. Determinants of low GS include: older age, shorter stature, low physical activity, poor nutrition, socioeconomic disadvantage and multimorbidity. Less is known about risk factors for accelerated loss of GS. We investigated determinants of level and 8-year loss of GS in 3703 men and women (aged 52–82 years) in the English Longitudinal Study of Ageing (ELSA). Four hundred and forty-one men and women (aged 59–71 years) who participated in a 10-year follow-up of the Hertfordshire Cohort Study (HCS) were used for replication. Variables were harmonised between cohorts. Change in GS was characterised using mixed-effects models in ELSA and a residual change approach in HCS and analysed for men and women combined. Men in ELSA and HCS had higher average levels of GS at baseline, and accelerated rates of loss, compared with women. In ELSA, older age, shorter stature and multimorbidity were correlated with lower level, and accelerated rate of loss, of GS in both sexes (accelerated loss of 0.04 (95% CI 0.00–0.08) standard deviation scores per additional morbidity after multivariable adjustment). Socioeconomic disadvantage, low level of physical activity and poorer self-reported health were also correlated with low GS level, but not loss rate, after multivariable adjustment. Analysis in HCS yielded similar results. Our results identify multimorbidity as a modifiable determinant of loss of muscle strength in later life, and raise the possibility that developmental influences may impact on rate of involutional decline in muscle strength

Mortality, bone density and grip strength: lessons from the past and hope for the future?

Lay Summary: What does this mean for patients? Low grip strength is important in the diagnosis of sarcopenia (loss of muscle mass and strength with age) and low bone density is used to define osteoporosis. Both sarcopenia and osteoporosis are common conditions among older people and are related to increased risk of poor health. In this study we examined grip strength and bone density in relation to the risk of death using data from older UK men and women from the Hertfordshire Cohort Study (aged 59–73 years at the start of the study). Lower grip strength was related to an increased risk of death (any cause) and death due to cardiovascular causes. In contrast, the relationships between bone density and risk of death (any cause) and death due to cardiovascular causes were weak. Relationships between muscle strength and risk of death were much stronger than the relationships between bone density and risk of death. This may reflect better treatment of low bone density, compared with low muscle strength, in this group of older people. This suggests that advances in the treatment of low muscle strength are required

Could self-reported physical performance help predict individuals at the highest risk of mortality and hospital admission events in clinical practice? Findings from the Hertfordshire Cohort Study

Aim: To consider how self-reported physical function measures relate to adverse clinical outcomes measured over 20 years of follow-up in a community-dwelling cohort (aged 59–73 at baseline) as compared with hand grip strength, a well-validated predictor of adverse events. Background: Recent evidence has emphasized the significant association of physical activity, physical performance, and muscle strength with hospital admissions in older people. However, physical performance tests require staff availability, training, specialized equipment, and space to perform them, often not feasible or realistic in the context of a busy clinical setting. Methods: In total, 2997 men and women were analyzed. Baseline predictors were measured grip strength (Jamar dynamometer) and the following self-reported measures: physical activity (Dallosso questionnaire); physical function score (SF-36 Health Survey); and walking speed. Participants were followed up from baseline (1998–2004) until December 2018 using UK Hospital Episode Statistics and mortality data, which report clinical outcomes using ICD-10 coding. Predictors in relation to the risk of mortality and hospital admission events were examined using Cox regression with and without adjustment for sociodemographic and lifestyle characteristics. Findings: The mean age at baseline was 65.7 and 66.6 years among men and women, respectively. Over follow-up, 36% of men and 26% of women died, while 93% of men and 92% of women were admitted to hospital at least once. Physical activity, grip strength, SF-36 physical function, and walking speed were all strongly associated with adverse health outcomes in both sex- and fully adjusted analyses; poorer values for each of the predictors were related to greater risk of mortality (all-cause, cardiovascular-related) and any, neurological, cardiovascular, respiratory, any fracture, and falls admissions. SF-36 physical function and grip strength were similarly associated with the adverse health outcomes considered

Multimorbidity and risk of falls, fractures, and joint replacements over two decades: Findings from the Hertfordshire Cohort Study

Aim: To examine the relationship between level of morbidity burden and long‐term risk of fractures, falls, and joint replacements in the community‐dwelling participants of the Hertfordshire Cohort Study. Methods: Data were analyzed from 2997 individuals (age 59–73 at baseline). Outcomes (fractures, falls, and lower limb joint replacements) were identified using ICD‐10 and OPCS‐4 codes from Hospital Episode Statistics data, available from baseline (1998–2004) until December 2018. Number of systems medicated (marker of morbidity level) in relation to risk of outcomes was examined using sex‐stratified Cox regression. Results: Among both men and women, a greater number of systems medicated was related to increased risk of falls (P < 0.001) and lower limb joint replacements (P < 0.003). More systems medicated was only related to increased risk of fracture among women (P‐values for trend of <0.001 among women and 0.186 among men). Conclusions: Higher morbidity was associated with increased risk of adverse health outcomes related to poor musculoskeletal health, but these relationships varied according to the musculoskeletal outcome studied. Intervention strategies to reduce multimorbidity among middle‐aged and older people may hence reduce the burden of musculoskeletal aging. Geriatr Gerontol Int 2024; ••: ••–••

Fracture Risk and Health Profiles Differ According to Relationship Status: Findings from the Hertfordshire Cohort Study

Registry studies have suggested associations between relationship status and fracture risk. We considered associations between relationship status and incident fracture in the Hertfordshire Cohort Study, comprising community-dwelling older adults, and explored associations between socioeconomic and lifestyle factors with relationship status. 2997 participants completed a baseline questionnaire (1998–2004) and clinic visit. Participants were followed up until December 2018 using Hospital Episode Statistics, which report clinical outcomes using codes from the 10th revision of the International Classification of Diseases (ICD-10); these codes were used to ascertain incident fractures. Relationship status (not currently married/cohabiting vs currently married/cohabiting) at baseline was examined in relation to incident fracture using Cox regression. Associations between baseline characteristics and relationship status were examined using logistic regression. Mean baseline age was 66.2 years. 80% were married/cohabiting at baseline; 15% had an incident fracture (mean (SD) follow-up duration: 14.4 (4.5) years). The following were related to greater likelihood of not being married/cohabiting: older age (women only); higher BMI (women only); current smoking; high alcohol consumption (men only); poorer diet quality (men only); lower physical activity; leaving school before age 15 (women only); and not owning one’s home. Those not married/cohabiting had greater risk of incident fracture compared to those who were (age-adjusted hazard ratios (95% CI) 1.58 (1.06, 2.38) among men, 1.35 (1.06, 1.72) among women); associations were attenuated after accounting for the above factors associated with relationship status in the corresponding sex. This suggests that differences in health profiles and lifestyle according to relationship status may explain the association between relationship status and fracture risk

Altered H19/miR‐675 expression in skeletal muscle is associated with low muscle mass in community‐dwelling older adults

Background: Despite increasing knowledge of the pathogenesis of muscle ageing, the molecular mechanisms are poorly understood. Based on an expression analysis of muscle biopsies from older Caucasian men, we undertook an in-depth analysis of the expression of the long non-coding RNA, H19, to identify molecular mechanisms that may contribute to the loss of muscle mass with age. Methods: We carried out transcriptome analysis of vastus lateralis muscle biopsies from 40 healthy Caucasian men aged 68–76 years from the Hertfordshire Sarcopenia Study (HSS) with respect to appendicular lean mass adjusted for height (ALMi). Validation and replication was carried out using qRT-PCR in 130 independent male and female participants aged 73–83 years recruited into an extension of the HSS (HSSe). DNA methylation was assessed using pyrosequencing. Results: Lower ALMi was associated with higher muscle H19 expression (r2 = 0.177, P < 0.001). The microRNAs, miR-675-5p/3p encoded by exon 1 of H19, were positively correlated with H19 expression (Pearson r = 0.192 and 0.182, respectively, P < 0.03), and miR-675-5p expression negatively associated with ALMi (r2 = 0.629, P = 0.005). The methylation of CpGs within the H19 imprinting control region (ICR) were negatively correlated with H19 expression (Pearson r = −0.211 to −0.245, P ≤ 0.05). Moreover, RNA and protein levels of SMAD1 and 5, targets of miR-675-3p, were negatively associated with miR-675-3p (r2 = 0.792 and 0.760, respectively) and miR-675-5p (r2 = 0.584 and 0.723, respectively) expression, and SMAD1 and 5 RNA levels positively associated with greater type II fibre size (r2 = 0.184 and 0.246, respectively, P < 0.05). Conclusions: Increased expression profiles of H19/miR-675-5p/3p and lower expression of the anabolic SMAD1/5 effectors of bone morphogenetic protein (BMP) signalling are associated with low muscle mass in older individuals

Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts

Background: Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited. Aim: We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors. Methods: Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4–6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell’s Concordance Index (C-index). Results: Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed. Conclusions: Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors

Risk factors for incident falls in older men and women:The English longitudinal study of ageing

Background: falls are a major cause of disability and death in older people, particularly women. Cross-sectional surveys suggest that some risk factors associated with a history of falls may be sex-specific, but whether risk factors for incident falls differ between the sexes is unclear. We investigated whether risk factors for incident falls differ between men and women.Methods: participants were 3298 people aged ≥60 who took part in the Waves 4-6 surveys of the English Longitudinal Study of Ageing. At Wave 4, they provided information about sociodemographic, lifestyle, behavioural and medical factors and had their physical and cognitive function assessed. Data on incident falls during the four-year follow-up period was collected from them at Waves 5 and 6. Poisson regression with robust variance estimation was used to derive relative risks (RR) for the association between baseline characteristics and incident falls.Results: in multivariable-adjusted models that also controlled for history of falls, older age was the only factor associated with increased risk of incident falls in both sexes. Some factors were only predictive of falls in one sex, namely more depressive symptoms (RR (95% CI) 1.03 (1.01,1.06)), incontinence (1.12 (1.00,1.24)) and never having married in women (1.26 (1.03,1.53)), and greater comorbidity (1.04 (1.00,1.08)), higher levels of pain (1.10 (1.04,1.17) and poorer balance, as indicated by inability to attempt a full-tandem stand, (1.23 (1.04,1.47)) in men. Of these, only the relationships between pain, balance and comorbidity and falls risk differed significantly by sex.Conclusions: there were some differences between the sexes in risk factors for incident falls. Our observation that associations between pain, balance and comorbidity and incident falls risk varied by sex needs further investigation in other cohorts. <br/

Extended and continuous decline in effective population size results in low genomic diversity in the world’s rarest hyena species, the brown hyena

Hyenas (family Hyaenidae), as the sister group to cats (family Felidae), represent a deeply diverging branch within the cat-like carnivores (Feliformia). With an estimated population size of <10,000 individuals worldwide, the brown hyena (Parahyaena brunnea) represents the rarest of the four extant hyena species and has been listed as Near Threatened by the IUCN. Here, we report a high-coverage genome from a captive bred brown hyena and both mitochondrial and low-coverage nuclear genomes of 14 wild-caught brown hyena individuals from across southern Africa. We find that brown hyena harbor extremely low genetic diversity on both the mitochondrial and nuclear level, most likely resulting from a continuous and ongoing decline in effective population size that started ∼1 Ma and dramatically accelerated towards the end of the Pleistocene. Despite the strikingly low genetic diversity, we find no evidence of inbreeding within the captive bred individual and reveal phylogeographic structure, suggesting the existence of several potential subpopulations within the species