Copy number variation associates with mortality in long-lived individuals:a genome-wide assessment

Pathophysiology, epidemiology and therapy of agein

Pro-inflammatory capacity of classically activated monocytes relates positively to muscle mass and strength

In mice, monocytes that exhibit a pro-inflammatory profile enter muscle tissue after muscle injury and are crucial for clearance of necrotic tissue and stimulation of muscle progenitor cell proliferation and differentiation. The aim of this study was to test if pro-inflammatory capacity of classically activated (M1) monocytes relates to muscle mass and strength in humans. This study included 191 male and 195 female subjects (mean age 64.2 years (SD 6.4) and 61.9 ± 6.4, respectively) of the Leiden Longevity Study. Pro-inflammatory capacity of M1 monocytes was assessed by ex vivo stimulation of whole blood with Toll-like receptor (TLR) 4 agonist lipopolysaccharide (LPS) and TLR-2/1 agonist tripalmitoyl-S-glycerylcysteine (Pam₃Cys-SK₄), both M1 phenotype activators. Cytokines that stimulate M1 monocyte response (IFN-γ and GM-CSF) as well as cytokines that are secreted by M1 monocytes (IL-6, TNF-α, IL-12, and IL-1β) were measured. Analyses were adjusted for age, height, and body fat mass. Upon stimulation with LPS, the cytokine production capacity of INF-γ, GM-CSF, and TNF-α was significantly positively associated with lean body mass, appendicular lean mass and handgrip strength in men, but not in women. Upon stimulation with Pam₃Cys-SK₄, IL-6; TNF-α; and Il-1β were significantly positively associated with lean body mass and appendicular lean in women, but not in men. Taken together, this study shows that higher pro-inflammatory capacity of M1 monocytes upon stimulation is associated with muscle characteristics and sex dependent

Accuracy of direct segmental multi-frequency bioimpedance analysis in the assessment of total body and segmental body composition in middle-aged adult population

SummaryBackground & aimsBody composition measurement is a valuable tool for assessing nutritional status and physical fitness in a variety of clinical settings. Although bioimpedance analysis (BIA) can easily assess body composition, its accuracy remains unclear. We examined the accuracy of direct segmental multi-frequency BIA technique (DSM-BIA) in assessing different body composition parameters, using dual energy X-ray absorptiometry (DEXA) as a reference standard.MethodsA total of 484 middle-aged participants from the Leiden Longevity Study were recruited. Agreements between DSM-BIA and DEXA for total and segmental body composition quantification were assessed using intraclass correlation coefficients and Bland–Altman plots.ResultsExcellent agreements were observed between both techniques in whole body lean mass (ICC female = 0.95, ICC men = 0.96), fat mass (ICC female = 0.97, ICC male = 0.93) and percentage body fat (ICC female = 0.93, ICC male = 0.88) measurements. Similarly, Bland–Altman plots revealed narrow limits of agreements with small biases noted for the whole body lean mass quantification but relatively wider limits for fat mass and percentage body fat quantifications. In segmental lean muscle mass quantification, excellent agreements between methods were demonstrated for the upper limbs (ICC female≥0.91, ICC men≥0.87) and lower limbs (ICC female≥0.83, ICC male≥0.85), with good agreements shown for the trunk measurements (ICC female = 0.73, ICC male = 0.70).ConclusionsDSM-BIA is a valid tool for the assessments of total body and segmental body composition in the general middle-aged population, particularly for the quantification of body lean mass

The number of p16INK4a positive cells in human skin reflects biological age

Cellular senescence is a defense mechanism in response to molecular damage which accumulates with aging. Correspondingly, the number of senescent cells has been reported to be greater in older than in younger subjects and furthermore associates with age-related pathologies. Inter-individual differences exist in the rate at which a person ages (biological age). Here, we studied whether younger biological age is related to fewer senescent cells in middle- aged individuals with the propensity for longevity, using p16INK4a as a marker for cellular senescence. We observed that a younger biological age associates with lower levels of p16INK4a positive cells in human skin

Gene expression analysis of mTOR pathway:Association with human longevity

mTOR signalling is implicated in the development of disease and in lifespan extension in model organisms. This pathway has been associated with human diseases such as diabetes and cancer, but has not been investigated for its impact on longevity per se. Here, we investigated whether transcriptional variation within the mTOR pathway is associated with human longevity using whole-blood samples from the Leiden Longevity Study. This is a unique cohort of Dutch families with extended survival across generations, decreased morbidity and beneficial metabolic profiles in middle-age. By comparing mRNA levels of nonagenarians and middle-aged controls, the mTOR signalling gene set was found to associate with old age (P=4.6×10-7). Single gene analysis showed that seven of 40 mTOR pathway genes had a significant differential expression of at least 5%. Of these, the RPTOR (Raptor) gene was found to be differentially expressed also when the offspring of nonagenarians was compared with their spouses, indicating association with familial longevity in middle-age. This association was not explained by variation between the groups in the prevalence of type 2 diabetes and cancer or glucose levels. Thus, the mTOR pathway not only plays a role in the regulation of disease and aging in animal models, but also in human health and longevity

An Internet-Based Physical Activity Intervention to Improve Quality of Life of Inactive Older Adults:A Randomized Controlled Trial

Pathophysiology, epidemiology and therapy of agein

Uncovering the Relationship between Selenium Status, Age, Health, and Dietary Habits: Insights from a Large Population Study including Nonagenarian Offspring from the MARK-AGE Project

An inadequate selenium (Se) status can accelerate the aging process, increasing the vulnerability to age-related diseases. The study aimed to investigate plasma Se and Se species in a large population, including 2200 older adults from the general population (RASIG), 514 nonagenarian offspring (GO), and 293 GO Spouses (SGO). Plasma Se levels in women exhibit an inverted U-shaped pattern, increasing with age until the post-menopausal period and then declining. Conversely, men exhibit a linear decline in plasma Se levels with age. Subjects from Finland had the highest plasma Se values, while those from Poland had the lowest ones. Plasma Se was influenced by fish and vitamin consumption, but there were no significant differences between RASIG, GO, and SGO. Plasma Se was positively associated with albumin, HDL, total cholesterol, fibrinogen, and triglycerides and negatively associated with homocysteine. Fractionation analysis showed that Se distribution among plasma selenoproteins is affected by age, glucometabolic and inflammatory factors, and being GO or SGO. These findings show that sex-specific, nutritional, and inflammatory factors play a crucial role in the regulation of Se plasma levels throughout the aging process and that the shared environment of GO and SGO plays a role in their distinctive Se fractionation