Skeletal Muscle Quality Of Nonagenarians And Centenarians

Skeletal muscle adipose tissue infiltration is hypothesized to lead to poorer muscle quality and function with aging. Indeed, skeletal muscle adiposity has emerged as a consistent, independent predictor of skeletal muscle strength, mobility, metabolic disorders, and survival among older adults. However, phenotypic features of skeletal muscle among the oldest-old remain poorly characterized. Herein, we evaluated the skeletal muscle characteristics of 54 nonagenarians and centenarians (mean age 98 years, range 90-110 years; 63% women) and 25 middle-aged individuals (mean age 54 years, range 40-59 years; 36% women) belonging to the Long Life Family Study (LLFS), an international, multicenter cohort of families with a clustering of longevity. Ultrasonography was used to measure echo intensity of the sternocleidomastoid muscle, which has a similar fiber type distribution to the rectus femoris. Greater echo intensity is indicative of lower muscle quality (greater adipose and fibrotic tissue). Current smoking, alcohol intake, and BMI were similar between the age groups. Nonagenarians and centenarians had lower grip strength (16.3 vs. 39 kg) and were less physically active (22.2% vs 66.7% exercised 1+ times per week) compared to younger individuals (P<0.001 for all). Mean±SE echo intensity, adjusted for gender, field center, BMI and physical activity was 52.1±1.7 among nonagenarians and centenarians compared to 44.2±2.4 among younger individuals (P=0.0098). Our preliminary findings suggest that nonagenarians and centenarians may have substantially lower skeletal muscle quality and strength compared to their younger aged counterparts. Additional research is needed to better understand the mechanisms leading to poorer muscle characteristics of the oldest-old.

Skeletal muscle adiposity and outcomes in candidates for lung transplantation: a lung transplant body composition cohort study

CT measurement of body composition may improve lung transplant candidate selection. We assessed whether skeletal muscle adipose deposition on abdominal and thigh CT scans was associated with 6 min walk distance (6MWD) and wait-list survival in lung transplant candidates. Each ½-SD decrease in abdominal muscle attenuation (indicating greater lipid content) was associated with 14 m decrease in 6MWD (95% CI −20 to −8) and 20% increased risk of death or delisting (95% CI 10% to 40%). Each ½-standard deviation decrease in thigh muscle attenuation was associated with 15 m decrease in 6MWD (95% CI −21 to −10). CT imaging may improve candidate risk stratification.

Wnt Pathway Inhibitor DKK1: A Potential Novel Biomarker for Adiposity

Emerging evidence indicates that ectopic skeletal muscle adiposity may be a risk factor for type 2 diabetes (T2D), especially in persons of African ancestry. In vitro studies suggest that a Wnt pathway inhibitor, Dickkopf-related protein 1 (DKK1), plays a role in adiposity regulation and could be a biomarker for adiposity in humans. The objective of this study was to test whether serum DKK1 levels relate to adiposity measures in a cohort from an African ancestry population at high risk for T2D. Fasting serum DKK1 was measured in a sample of 159 men of African ancestry aged ≥40 years (mean age ± SD, 63.5 ± 8.2 years; mean body mass index, 27.8 ± 4.5 kg/m2). Anthropometrics included total-body and trunk adiposity measured by dual-energy x-ray absorptiometry and lower-leg skeletal muscle density measured by CT [which reflects the intramuscular adiposity content (mg/cm3)]. Serum DKK1 was positively correlated with BMI (r = 0.20; P = 0.01), waist circumference (r = 0.15; P = 0.046), DXA total-body adiposity (r = 0.24; P = 0.003), and DXA trunk adiposity (r = 0.21; P = 0.009), independent of age and height. In addition, serum DKK1 was inversely correlated with skeletal muscle density (r = −0.25; P = 0.002), independent of age, BMI, and calf muscle area. No significant correlation was found between serum DKK1 and fasting serum glucose or insulin levels or insulin resistance estimated by homeostasis model assessment. These findings suggest that higher levels of serum DKK1 may be associated with greater overall, central, and ectopic skeletal muscle adiposity. Further studies are needed to unravel the potential role of DKK1 in the regulation of adiposity in humans.

Abstract MP048: Ectopic Muscle and Liver Adiposity are Independently Associated with Type 2 Diabetes in African Ancestry Men

Although obesity is a major driver of type 2 diabetes (T2D), many obese individuals do not develop T2D. Indeed, fat around and within non-adipose tissue organs (i.e., ectopic fat) is emerging as a strong risk factor for diabetes. The potential differential contribution of ectopic fat depots throughout the body on T2D risk is unclear because studies have mainly focused on visceral and/or liver fat. No study, to our knowledge, has addressed the potential independent association of visceral, liver, and skeletal muscle adiposity with T2D. Such studies are particularly needed among African ancestry populations, as generalized obesity and other risk factors do not appear to explain the high T2D burden in this population segment. To address this knowledge gap, we measured total body fat by DXA, and visceral, liver, and calf skeletal muscle adiposity by computed tomography in 490 Afro-Caribbean men, aged 50-91 years (mean age=64 years, mean BMI=27.5 kg/m 2 ). The prevalence of T2D in this population was 22.3%. We employed multiple logistic regression using total body fat percent and ectopic fat depots as predictors (Table). We found that each 7.9 HU decrease in liver attenuation (indicative of greater liver adiposity) was associated with a 33% increased odds of T2D (p=0.011). Similarly, each 4.2 mg/cm 3 decrease in muscle attenuation (indicative of greater intra-muscular adiposity) was associated with a 31% increased odds of T2D (p=0.04). These associations were independent of total and visceral adiposity. Our results support the “ectopic fat syndrome” theory, as opposed to the “portal theory”, in the pathogenesis of diabetes among African ancestry men. Longitudinal studies are needed to clarify the exact role of specific ectopic fat depots in T2D, particularly in high-risk African ancestry populations.