Body composition parameters and sarcopenia in adults with Down syndrome: a case-control study.

BACKGROUND: Individuals with Down syndrome (DS) experience premature aging. Whether accelerated aging involves changes in body composition parameters and is associated with early development of sarcopenia is unclear. AIMS: To compare parameters of body composition and the prevalence of sarcopenia between adults with DS and the general population. METHODS: Body composition was assessed by whole-body dual-energy X-ray absorptiometry (DXA). Fat mass (FMI) and skeletal mass indices (SMI) were calculated as the ratio between total body fat mass and appendicular lean mass and the square of height, respectively. Fat mass distribution was assessed by the android/gynoid fat ratio (A/G). Sarcopenia was defined according to the criteria and cut-points recommended by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Data on age- and sex-matched non-DS controls were retrieved from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) population. RESULTS: Sixty-four DS adults (mean age 37.2 ± 12.0 years, 20.3% women) were enrolled and compared with age- and sex-matched NHANES participants (n = 256), in a 1:4 ratio. FMI (7.96 ± 3.18 kg/m2 vs. 8.92 ± 4.83 kg/m2, p = 0.135), SMI (7.38 ± 1.01 kg/m2 vs. 7.46 ± 2.77 kg/m2, p = 0.825) and A/G (0.98 ± 0.17 vs. 1.01 ± 0.22, p = 0.115) were not significantly different between DS and control participants. When the sample was stratified by sex, women with DS had a higher FMI compared with their NHANES controls (10.16 ± 4.35 kg/m2 vs. 8.11 ± 4.29 kg/m2, p < 0.001), while men with DS had lower A/G ratio (1.04 ± 0.16 vs. 1.11 ± 0.22, p = 0.002). Sarcopenia was more frequent in individuals with DS than in controls (35.6% vs. 19.9%, p = 0.007). This association was stronger in men 40 years and older. CONCLUSIONS: Adults with DS have a higher prevalence of sarcopenia compared with the general population. This finding suggests that DS is associated with early muscle aging and calls for the design of interventions targeting the skeletal muscle to prevent or treat sarcopenia.

Intrinsic capacity and recent falls in adults 80 years and older living in the community: results from the ilSIRENTE Study.

BACKGROUND: Falls in older adults significantly impact overall health and healthcare costs. Intrinsic capacity (IC) reflects functional reserve and is an indicator of healthy aging. AIMS: To explore the association between IC and recent falls (≤ 90 days) in community-dwelling octogenarians from the Aging and Longevity in the Sirente geographic area (IlSIRENTE) study. METHODS: The Minimum Data Set for Home Care (MDS-HC) and supplementary questionnaires and tests were used to assess the five IC domains: locomotion, cognition, vitality, psychology, and sensory. Scores in each domain were rescaled using the percent of maximum possible score method and averaged to obtain an overall IC score (range 0-100). RESULTS: The study included 319 participants (mean age 85.5 ± 4.8 years, 67.1% women). Mean IC score was 80.5 ± 14.2. The optimal IC score cut-off for predicting the two-year risk of incident loss of at least one activity of daily living (ADL) was determined and validated in a subset of 240 individuals without ADL disability at baseline (mean age 84.7 ± 4.4 years, 67.1% women). Participants were then stratified into low (< 77.6) and high (≥ 77.6) IC categories. Those with high IC (63.9%) were younger, more often males, and had lower prevalence of recent falls, disability, multimorbidity, and polypharmacy. Logistic regression models including IC as a continuous variable revealed a significant association between higher IC and lower odds of falls. This association was significant in the unadjusted (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94-0.98, p < 0.001), age- and sex-adjusted (OR 0.96, 95% CI 0.94-0.98, p < 0.001), and fully adjusted models (OR 0.96, 95% CI 0.93-0.99, p = 0.003). When considering IC as a categorical variable, unadjusted logistic regression showed a strong association between high IC and lower odds of falls (OR 0.31, 95% CI 0.16-0.60, p < 0.001). This association remained significant in both the age- and sex-adjusted (OR 0.30, 95% CI 0.15-0.59, p < 0.001) and fully adjusted models (OR 0.33, 95% CI 0.16-0.82, p = 0.007). The locomotion domain was independently associated with falls in the unadjusted (OR 0.98, 95% CI 0.97-0.99, p < 0.001), age- and sex-adjusted (OR 0.97, 95% CI 0.96-0.99, p < 0.001), and fully adjusted model (OR 0.98, 95% CI 0.96-0.99, p < 0.001). DISCUSSION: This is the first study using an MDS-HC-derived instrument to assess IC. Individuals with higher IC were less likely to report recent falls, with locomotion being an independently associated domain. CONCLUSIONS: Lower IC is linked to increased odds of falls. Interventions to maintain and improve IC, especially the locomotion domain, may reduce fall risk in community-dwelling octogenarians.

Physical performance and negative events in very old adults: a longitudinal study examining the ilSIRENTE cohort.

BACKGROUND: Declining physical performance in old age is associated with a wide range of negative health-related outcomes. However, it is unclear which physical capabilities should be prioritized to obtain prognostic information in older adults. AIMS: To examine the associations between the performance on several physical function tests and falls, disability, and death in a well-characterized sample of very old Italian adults. METHODS: This was a prospective cohort study of older adults who lived in the mountain community of the Sirente geographic area in Central Italy. Physical performance was assessed using isometric handgrip strength (IHG), walking speed (WS) at a usual and fast pace, 5-time sit-to-stand test (5STS), and sit-to-stand power measures. Appendicular skeletal muscle mass was estimated from calf circumference using a validated equation. History of falls, incident falls, and disability status according to basic Activities of Daily Living (ADLs) were recorded over two years. Survival status was obtained from the participants' general practitioners and was confirmed by the National Death Registry over 10 years from enrolment. Linear, binary, and Cox regressions were performed to evaluate the association between physical performance measures and health outcomes. RESULTS: The mean age of the 255 participants was 84.2 ± 5.1 years, and 161 (63.1%) were women. Logistic regression indicated that IHG was significantly associated with incident ADL disability, whereas specific sit-to-stand muscle power was an independent predictor of death. No significant associations were observed between physical function and falls. CONCLUSIONS: Our findings indicate selective associations between physical function tests and the occurrence of negative events in very old adults, with poor IHG predicting disability and specific sit-to-stand muscle power being longitudinally associated with death.

Mitochondrial Quantity and Quality in Age-Related Sarcopenia.

Sarcopenia, the age-associated decline in skeletal muscle mass and strength, is a condition with a complex pathophysiology. Among the factors underlying the development of sarcopenia are the progressive demise of motor neurons, the transition from fast to slow myosin isoform (type II to type I fiber switch), and the decrease in satellite cell number and function. Mitochondrial dysfunction has been indicated as a key contributor to skeletal myocyte decline and loss of physical performance with aging. Several systems have been implicated in the regulation of muscle plasticity and trophism such as the fine-tuned and complex regulation between the stimulator of protein synthesis, mechanistic target of rapamycin (mTOR), and the inhibitor of mTOR, AMP-activated protein kinase (AMPK), that promotes muscle catabolism. Here, we provide an overview of the molecular mechanisms linking mitochondrial signaling and quality with muscle homeostasis and performance and discuss the main pathways elicited by their imbalance during age-related muscle wasting. We also discuss lifestyle interventions (i.e., physical exercise and nutrition) that may be exploited to preserve mitochondrial function in the aged muscle. Finally, we illustrate the emerging possibility of rescuing muscle tissue homeostasis through mitochondrial transplantation.

Mitochondrial Quality Control Processes at the Crossroads of Cell Death and Survival: Mechanisms and Signaling Pathways.

Biological aging results from an accumulation of damage in the face of reduced resilience. One major driver of aging is cell senescence, a state in which cells remain viable but lose their proliferative capacity, undergo metabolic alterations, and become resistant to apoptosis. This is accompanied by complex cellular changes that enable the development of a senescence-associated secretory phenotype (SASP). Mitochondria, organelles involved in energy provision and activities essential for regulating cell survival and death, are negatively impacted by aging. The age-associated decline in mitochondrial function is also accompanied by the development of chronic low-grade sterile inflammation. The latter shares some features and mediators with the SASP. Indeed, the unloading of damage-associated molecular patterns (DAMPs) at the extracellular level can trigger sterile inflammatory responses and mitochondria can contribute to the generation of DAMPs with pro-inflammatory properties. The extrusion of mitochondrial DNA (mtDNA) via mitochondrial outer membrane permeabilization under an apoptotic stress triggers senescence programs. Additional pathways can contribute to sterile inflammation. For instance, pyroptosis is a caspase-dependent inducer of systemic inflammation, which is also elicited by mtDNA release and contributes to aging. Herein, we overview the molecular mechanisms that may link mitochondrial dyshomeostasis, pyroptosis, sterile inflammation, and senescence and discuss how these contribute to aging and could be exploited as molecular targets for alleviating the cell damage burden and achieving healthy longevity.

Restoring Mitochondrial Function and Muscle Satellite Cell Signaling: Remedies against Age-Related Sarcopenia.

Sarcopenia has a complex pathophysiology that encompasses metabolic dysregulation and muscle ultrastructural changes. Among the drivers of intracellular and ultrastructural changes of muscle fibers in sarcopenia, mitochondria and their quality control pathways play relevant roles. Mononucleated muscle stem cells/satellite cells (MSCs) have been attributed a critical role in muscle repair after an injury. The involvement of mitochondria in supporting MSC-directed muscle repair is unclear. There is evidence that a reduction in mitochondrial biogenesis blunts muscle repair, thus indicating that the delivery of functional mitochondria to injured muscles can be harnessed to limit muscle fibrosis and enhance restoration of muscle function. Injection of autologous respiration-competent mitochondria from uninjured sites to damaged tissue has been shown to reduce infarct size and enhance cell survival in preclinical models of ischemia-reperfusion. Furthermore, the incorporation of donor mitochondria into MSCs enhances lung and cardiac tissue repair. This strategy has also been tested for regeneration purposes in traumatic muscle injuries. Indeed, the systemic delivery of mitochondria promotes muscle regeneration and restores muscle mass and function while reducing fibrosis during recovery after an injury. In this review, we discuss the contribution of altered MSC function to sarcopenia and illustrate the prospect of harnessing mitochondrial delivery and restoration of MSCs as a therapeutic strategy against age-related sarcopenia.

Diagnostic and prognostic value of calf circumference for sarcopenia in community-dwelling older adults.

BACKGROUND: An age-dependent normative values of calf circumference (CC) has been recently proposed as an accessible proxy for muscle mass. However, its usefulness to estimate sarcopenia has not been assessed. The objectives of the present study were to determine if the substitution of the classical way to assess muscle mass by these values have enough diagnostic accuracy and prognostic value among older adults living in the community. METHODS: Data from the Toledo Study of Healthy Ageing (TSHA) were used. CC was measured using an anthropometric tape. We used two age-groups CC cut-off points: the TSHA CC median and the one proposed in the Longevity Check-up 7+ (Lookup 7+) project. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People (EWGSOP2), the Foundation for the National Institutes of Health (FNIH), and FNIH criteria standardized for our population (sFNIH). Frailty (according to the Frailty Phenotype and the Frailty Trait Scale-5) and disability (Katz index) were assessed at baseline and follow-up. Mortality and first hospitalization were also recorded. Logistic (incident frailty and worsening disability) and Cox (mortality and hospitalization) regressions were performed. Diagnostic accuracy was assessed through Kappa index, AUCs, positive and negative predictive values. Predictive ability was assessed through AUCs and integrated AUCs (IAUCs). RESULTS: 1531 participants (74.8 ± 5.8 years; 45.6% men) were included in the analysis. Prevalence rates of sarcopenia were 22.7% (sFNIH), 15.0% (FNIH), and 13.9% (EWGSOP2). Using TSHA-based cut-points of CC, the prevalence of sarcopenia was 16.8% (sFNIH), 11.0% (FNIH), and 11.5% (EWGSOP2). According to LC7+-based CC cut-off points, sarcopenia prevalence was 17.6% (sFNIH), 11.9% (FNIH), and 12.4% (EWGSOP2). CC cut-off points showed low-to-moderate agreement (Kappa Index values between 0.49 and 0.69) with appendicular lean mass for the evaluation of sarcopenia. Sarcopenia identified by Lookup 7+ and TSHA CC cut-off points was associated with the adverse events examined, with similar AUCs and IAUCs than original sarcopenia definitions, and were lost after adjustment by baseline frailty, except when the original EWGSOP2 definition was used. CONCLUSIONS: Using normalized values of CC as a criteria of muscle mass shows moderate agreement with classical criteria for diagnosing sarcopenia and offer similar predictive value in community-dwelling older adults.

Predictive values of relative fat mass and body mass index on cardiovascular health in community-dwelling older adults: Results from the Longevity Check-up (Lookup) 7.

OBJECTIVES: To assess the predictive value of relative fat mass compared to body mass index for hypertension, diabetes, hyperlipidemia, and heightened cardiovascular risk in a cohort of community-dwelling older adults from the Longevity Check-up 7+ cohort. STUDY DESIGN: Retrospective cross-sectional study. MAIN OUTCOME MEASURES: Hyperlipidemia was defined as total cholesterol ≥200 mg/dL or ongoing lipid-lowering treatment. Diabetes was defined either as self-reported diagnosis or fasting blood glucose >126 mg/dL or a random blood glucose >200 mg/dL. Hypertension was defined as blood pressure ≥ 140/90 mmHg or requiring daily antihypertensive medications. Heightened cardiovascular risk was operationalized as having at least two of these conditions. RESULTS: Analyses were conducted in 1990 participants (mean age 73.2 ± 6.0 years; 54.1 % women). Higher proportions of men than women had hypertension and diabetes, while hyperlipidemia was more prevalent in women. Receiver operating curve analysis indicated relative fat mass was a better predictor of hypertension in women and diabetes in both sexes. Body mass index performed better in predicting hyperlipidemia in women. Relative fat mass thresholds of ≥27 % for men and ≥40 % for women were identified as optimal indicators of heightened cardiovascular risk and so were used to defined high adiposity. Moderate correlations were found between high adiposity or body mass index ≥25 kg/m2 and the presence of hypertension, hyperlipidemia and heightened cardiovascular risk, while a strong correlation was found with diabetes. Logistic regression analysis highlighted significant associations between high adiposity and increased odds of hypertension, diabetes, and heightened cardiovascular risk. CONCLUSIONS: Proposed cut-offs for relative fat mass were more reliable indices than the usual cut-offs for body mass index for identifying individuals at heightened cardiovascular risk. Our findings support the role of anthropometric measures in evaluating body composition and the associated metabolic and cardiovascular conditions in older adults.

Associations between hypertension and cognitive, mood, and behavioral parameters in very old adults: results from the IlSIRENTE study.

Introduction: Studies on the associations between hypertension-related parameters and cognitive function, mood, and behavioral symptoms in older adults have produced mixed findings. A possible explanation for these divergent results is that investigations have not adequately adjusted their analyses according to the use of angiotensin-converting enzyme inhibitors (ACEIs). Therefore, the present study examined the cross-sectional associations between hypertension-related parameters, ACEI use, and cognitive function, mood, and behavioral symptoms in very old adults. Methods: This study was conducted by analyzing the IlSIRENTE database, a prospective cohort study that collected data on all individuals aged 80 years and older residing in the Sirente geographic area (n = 364). Blood pressure (BP) was assessed after 20 to 40 min of rest, while participants sat in an upright position. Drugs were coded according to the Anatomical Therapeutic and Chemical codes. Cognitive function, mood, and behavioral symptoms were recorded using the Minimum Data Set Home Care instrument. Blood inflammatory markers were measured. Results: Hypertension-related parameters were significantly associated with many cognitive, mood, and behavioral parameters after adjustment for covariates. However, only the inverse association between hypertension and lesser problems with short-term memory remained significant. Participants with hypertension had lower blood concentrations of inflammatory markers in comparison to their normotensive peers. Conclusion: Findings from the present study indicate that high BP values are associated with fewer complaints about memory problems in very old adults. Furthermore, a lower concentration of inflammatory markers was found in hypertensive participants. ACEI use might affect this scenario.

Association of Physical Activity and Exercise with Physical Performance and Muscle Mass in Older Adults: Results from the Longevity Check-Up (Lookup) 7+ Project.

Regular engagement in physical activity (PA) or physical exercise (PE) is effective at improving physical performance and body composition in older adults. Less is known about the benefits that may be obtained through combining PA with PE and whether the effects of activity habits differ between men and women. This study cross-sectionally investigated the association of PA and/or PE with physical performance and anthropometric measures in a large and relatively unselected sample of older adults enrolled in the Longevity Check-up (Lookup) 7+ project. Participants were individuals 65 years and older living in the community who were recruited in unconventional settings across Italy. Adherence to PA or PE was operationalized as involvement in light walking or various types of exercise, respectively, at least twice weekly for a minimum of 30 min per session throughout the last 12 months. Physical performance measures included handgrip strength and five-time sit-to-stand (5STS) tests. Lower-limb muscle power and appendicular skeletal muscle mass (ASM) were estimated through validated equations. We analyzed data of 4119 participants, of whom 2222 (53.4%) were women. The mean age was 72.8 ± 5.8 years in men and 72.1 ± 5.4 years in women. Regular engagement in PA + PE was reported by 139 (7.3%) men and 100 (4.5%) women. Results indicated that regular walking activity and/or PE were significantly associated with better physical performance and greater ASM with sex-specific patterns. Associations were also influenced by the type of activity, physical performance assessment tool, and anthropometric parameters. Men engaged in PA + PE performed better on the 5STS test and had greater handgrip strength, ASM, and relative and specific muscle power than those practicing either PA or PE. In women, the combination of PA and PE was associated with greater handgrip strength. The findings of this study indicate that older adults regularly practicing PA + PE had better physical performance than those who only engaged in either modality. In men, the combination of PA and PE was also associated with greater ASM.