Lipoprotein Particle Profiles Mark Familial and Sporadic Human Longevity

BACKGROUND: Genetic and biochemical studies have indicated an important role for lipid metabolism in human longevity. Ashkenazi Jewish centenarians and their offspring have large low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles as compared with control individuals. This profile also coincided with a lower prevalence of disease. Here, we investigate whether this observation can be confirmed for familial longevity in an outbred European population and whether it can be extended to sporadic longevity in the general population. METHODS AND FINDINGS: NMR-measured lipoprotein profiles were analyzed in 165 families from the Leiden Longevity Study, consisting of 340 long-lived siblings (females >91 y, males >89 y), 511 of their offspring, and 243 partners of the offspring. Offspring had larger (21.3 versus 21.1 nm; p = 0.020) and fewer (1,470 versus 1,561 nmol/l; p = 0.011) LDL particles than their same-aged partners. This effect was even more prominent in the long-lived siblings (p < 10(−3)) and could be pinpointed to a reduction specifically in the concentration of small LDL particles. No differences were observed for HDL particle phenotypes. The mean LDL particle sizes in 259 90-y-old singletons from a population-based study were similar to those in the long-lived siblings and thus significantly larger than in partners of the offspring, suggesting that the relevance of this phenotype extends beyond familial longevity. A low concentration of small LDL particles was associated with better overall health among both long-lived siblings (p = 0.003) and 90-y-old singletons (p = 0.007). CONCLUSIONS: Our study indicates that LDL particle profiles mark both familial and sporadic human longevity already in middle age

The case for strategic international alliances to harness nutritional genomics for public and personal health

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countrie

Being Active, Engaged, and Healthy:Older Persons' Plans and Wishes to Age Successfully

Objectives: This study took an emic multidimensional approach on successful aging and examined what older people consider important to age successfully by asking them about their plans and wishes (PWs). Associations between participants' demographics, health status, working life, social contacts, life satisfaction, and their PWs were investigated. Method: An online questionnaire was completed by 649 older individuals (55-90 years). Conceptual content analysis was performed to identify important categories in PWs. Quantitative analyses were conducted to examine associations between PWs and participants' characteristics. Results: Most mentioned PWs were related to activities, engagement with life, and health. Seventy-four participants (11.4%) expressed no PWs. Multivariate analysis revealed that having PWs was most strongly related to participants' life satisfaction. Older individuals with a higher life satisfaction indicated significantly more often to have PWs than individuals with a lower life satisfaction. Discussion: The majority of older people desire an active, engaged, and healthy life. PWs were variable and personal, which endorses an emic, multidimensional approach to successful aging. Knowledge on what older individuals find important in their lives and what they want to achieve can assist older individuals in setting and attaining their goals toward aging well

Ambulant 24-h glucose rhythms mark calendar and biological age in apparently healthy individuals

Glucose metabolism marks health and disease and is causally inferred in the aging process. Ambulant continuous glucose monitoring provides 24-h glucose rhythms under daily life conditions. We aimed to describe ambulant 24-h glucose rhythms measured under daily life condition in relation to calendar and biological age in apparently healthy individuals. In the general population and families with propensity for longevity, we studied parameters from 24-h glucose rhythms; glucose levels; and its variability, obtained by continuous glucose monitoring. Participants were 21 young (aged 22-37 years), 37 middle-aged (aged 44-72 years) individuals from the general population, and 26 middle-aged (aged 52-74 years) individuals with propensity for longevity. All were free of diabetes. Compared with young individuals, middle-aged individuals from the general population had higher mean glucose levels (5.3 vs. 4.7 mmol L(-1) ,

Ambulant 24-h glucose rhythms mark calendar and biological age in apparently healthy individuals

Abstract Glucose metabolism marks health and disease and is causally inferred in the aging process. Ambulant continuous glucose monitoring provides 24-h glucose rhythms under daily life conditions. We aimed to describe ambulant 24-h glucose rhythms measured under daily life condition in relation to calendar and biological age in apparently healthy individuals. In the general population and families with propensity for longevity, we studied parameters from 24-h glucose rhythms; glucose levels; and its variability, obtained by continuous glucose monitoring. Participants were 21 young (aged 22-37 years), 37 middle-aged (aged 44-72 years) individuals from the general population, and 26 middle-aged (aged 52-74 years) individuals with propensity for longevity. All were free of diabetes. Compared with young individuals, middle-aged individuals from the general population had higher mean glucose levels (5.3 vs. 4.7 mmol L À1 , P &lt; 0.001), both diurnally (P &lt; 0.001) and nocturnally (P = 0.002). Glucose variability was higher in the middle-aged compared with the young (standard deviation 0.70 vs. 0.57 mmol L À1 , P = 0.025). Compared with middle-aged individuals from the general population, middle-aged individuals with propensity for longevity had lower overall mean glucose levels (5.2 vs. 5.4 mmol L À1 , P = 0.047), which were more different nocturnally (4.8 vs. mmol L À1 , P = 0.003) than diurnally (5.3 vs. 5.5 mmol L À1 , P = 0.14). There were no differences in glucose variability between these groups. Results were independent of body mass index. Among individuals without diabetes, we observed significantly different 24-h glucose rhythms depending on calendar and biological age

Timing of objectively-collected physical activity in relation to body weight and metabolic health in sedentary older people: a cross-sectional and prospective analysis

Background: Little is known about the impact of timing as opposed to frequency and intensity of daily physical activity on metabolic health. Therefore, we assessed the association between accelerometery-based daily timing of physical activity and measures of metabolic health in sedentary older people. Methods: Hourly mean physical activity derived from wrist-worn accelerometers over a 6-day period was collected at baseline and after 3 months in sedentary participants from the Active and Healthy Ageing study. A principal component analysis (PCA) was performed to reduce the number of dimensions (e.g. define periods instead of separate hours) of hourly physical activity at baseline and change during follow-up. Cross-sectionally, a multivariable-adjusted linear regression analysis was used to associate the principal components, particularly correlated with increased physical activity in data-driven periods during the day, with body mass index (BMI), fasting glucose and insulin, HbA1c and the homeostatic model assessment for insulin resistance (HOMA-IR). For the longitudinal analyses, we calculated the hourly changes in physical activity and change in metabolic health after follow-up. Results: We included 207 individuals (61.4% male, mean age: 64.8 [SD 2.9], mean BMI: 28.9 [4.7]). Higher physical activity in the early morning was associated with lower fasting glucose (−2.22%, 95% CI: −4.19, −0.40), fasting insulin (−13.54%, 95%CI: −23.49, −4.39), and HOMA-IR (−16.07%, 95%CI: −27.63, −5.65). Higher physical activity in the late afternoon to evening was associated with lower BMI (−2.84%, 95% CI: −4.92, −0.70). Higher physical activity at night was associated with higher BMI (2.86%, 95% CI: 0.90, 4.78), fasting glucose (2.57%, 95% CI: 0.70, 4.30), and HbA1c (2.37%, 95% CI: 1.00, 3.82). Similar results were present in the prospective analysis. Conclusion: Specific physical activity timing patterns were associated with more beneficial metabolic health, suggesting particular time-dependent physical activity interventions might maximise health benefits.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Support Biomechanical Engineerin

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

A Genomewide Association Study of Skin Pigmentation in a South Asian Population

We have conducted a multistage genomewide association study, using 1,620,742 single-nucleotide polymorphisms to systematically investigate the genetic factors influencing intrinsic skin pigmentation in a population of South Asian descent. Polymorphisms in three genes—SLC24A5, TYR, and SLC45A2—yielded highly significant replicated associations with skin-reflectance measurements, an indirect measure of melanin content in the skin. The associations detected in these three genes, in an additive manner, collectively account for a large fraction of the natural variation of skin pigmentation in a South Asian population. Our study is the first to interrogate polymorphisms across the genome, to find genetic determinants of the natural variation of skin pigmentation within a human population

Study Design

<p>Long-lived families were recruited if they included a long-lived sibling pair with males aged 89 y or older and women aged 91 y or older.</p