Genomic Variation and Pharmacokinetics in Old Age: A Quantitative Review of Age- vs. Genotype-Related Differences.
Ontology highlight
ABSTRACT:
SUBMITTER: Ducker CM
PROVIDER: S-EPMC6585622 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
Publications
Genomic Variation and Pharmacokinetics in Old Age: A Quantitative Review of Age- vs. Genotype-Related Differences.
Dücker Christof M CM Brockmöller Jürgen J
Clinical pharmacology and therapeutics 20180402 3
Older persons may particularly benefit from pharmacogenetic diagnostics, but there is little clinical evidence on that question. We quantitatively analyzed the effects of age and genotype in drugs with consensus on a therapeutically relevant impact of a genotype. Assuming additive effects of age and genotype, drugs may be classified in groups with different priorities to consider either age, or genotype, or both, in therapy. Particularly interesting were those studies specifically analyzing the ...[more]
Similar Datasets
Project description:Aging is known to have deleterious effects on cerebral white matter, yet little is known about these white matter alterations in advanced age. In this study, 94 oldest-old adults without dementia (90-103 years) underwent diffusion tensor imaging to assess relationships between chronological age and multiple measures of integrity in 18 white matter regions across the brain. Results revealed significant age-related declines in integrity in regions previously identified as being sensitive to aging in younger-old adults (corpus callosum, fornix, cingulum, external capsule). For the corpus callosum, the effect of age on genu fractional anisotropy was significantly weaker than the relationship between age and splenium fractional anisotropy. Importantly, age-related declines in white matter integrity did not differ in cognitively normal and cognitively impaired not demented oldest-old, suggesting that they were not solely driven by cognitive dysfunction or preclinical dementia in this advanced age group. Instead, white matter in these regions appears to remain vulnerable to normal aging processes through the 10th decade of life.
| S-EPMC5647141 | biostudies-literature
Project description:BackgroundMuscle flexibility is a main component of health-related fitness and one of the basic components of fitness for the performance in some sports. Sport and health professionals require the flexibility profile of soccer to define quantitative aims in the training of flexibility. The aim of this study was to identify age-related differences in lower extremity flexibility in youth soccer players.MethodsSeventy-two young male soccer players (age: 13.0 ± 3.1 y; body mass: 50.5 ± 15.3 kg; stature 158.2 ± 16.8 cm; BMI: 19.6 ± 2.6 kg/m2) completed this study. Measures of eleven passive hip (hip extension (HE), hip adduction with hip flexed 90°(HAD-HF90°), hip flexion with knee flexed (HF-KF) and extended (HF-KE), hip abduction with hip neutral (HAB) and hip flexed 90°(HAB-HF90°), hip external (HER) and internal (HIR) rotation), knee (knee flexion (KF)) and ankle dorsiflexion (ankle dorsiflexion with knee flexed (ADF-KF) and extended (ADF-KE)) ranges of motion (ROM) were taken. Descriptive statistics were calculated for hip, knee and ankle ROM measured separately by leg (dominant and non-dominant) and age-group (U10, U12, U14, U16 and U19). The data was analysed using a one-way analysis of variance (ANOVA) to examine the interaction of 11 ROM in the different players' age-group.ResultsGenerally, U10 and/or U12 soccer players obtain the highest mean value in almost all ROM evaluated (U10: HAD-HF [39.6° ± 4.3°], ADF-KE [32.3° ± 4.1°], HER [63.5° ± 5.6°] and HAB-HF90°[64.1° ± 7.5°]; U12: HE [17.7° ± 6.2°], HAB [35.6° ± 3.0], HIR [60.8° ± 4.7°] and KF [133.8° ± 7.1°]). Nonetheless, significant differences between the players' age-groups are just found in HAD-HF90°(p = .042; ES = .136), HAB (p = .001; ES = .252), HIR (p = .001; ES = .251), HER (p < .001; ES = .321) and HAB-HF90°(p < .001; ES = .376) ROM, showing a progressive and irregular decrease in these ROM until the U19 team.ConclusionThe findings of this study reinforce the necessity of prescribing exercises aimed at improving HAD-HF90° ROM in U16, HAB ROM in U14, HIR ROM in U16 and U19, HER ROM in U12 and U19, and HAB-HF90° ROM in U16 and U19 players within everyday soccer training routines.
| S-EPMC6357869 | biostudies-literature
Project description:ObjectivesTo characterize the effects of CYP2B6 polymorphisms, diurnal variation and demographic factors on nevirapine pharmacokinetics in African children.MethodsNon-linear mixed-effects modelling conducted in NONMEM 7.3 described nevirapine plasma concentration-time data from 414 children aged 0.3-15 years.ResultsNevirapine pharmacokinetics was best described using a one-compartment disposition model with elimination through a well-stirred liver model accounting for a first-pass effect and transit-compartment absorption. Intrinsic clearance was affected by diurnal variation (characterized using a cosine function with peak amplitude 29% at 12 noon) and CYP2B6 metabolizer status [extensive metabolizer (EM) 516GG|983TT, reference; intermediate metabolizer (IM) 516GT|983TT or 516GG|983TC, 17% lower; slow metabolizer (SM) 516TT|983TT or 516GT|983TC, 50% lower; ultra-slow metabolizer (USM) 516GG|983CC, 68% lower]. Age was found to affect pre-hepatic bioavailability: 31.7% lower at birth and increasing exponentially. Median (90% CI) evening Cmin values in the different metabolizer groups were 5.01 (3.01-7.47), 6.55 (3.65-13.32), 11.59 (5.44-22.71) and 12.32 (12.32-27.25) mg/L, respectively. Evening Cmin values were <3 mg/L in 43% of EM weighing <6 kg and 26% of IM weighing <6 kg, while 73% of SM and 88% of USM in all weight-bands had evening Cmin values >8 mg/L. Cmin was not markedly affected by administration time, but was altered by unequal splitting of the daily dose.ConclusionsDiurnal variation does not greatly affect nevirapine exposure. However, when daily doses cannot be split equally, the larger dose should be given in the morning. To achieve homogeneous exposures, nevirapine doses for SM and USM should be reduced by 50%, and children weighing <6 kg with EM or IM metabolizer status should receive the same dose as children weighing 6-10 kg.
| S-EPMC5161049 | biostudies-literature
Project description:Contrary to common stereotypes, loneliness is not restricted to old age but can occur at any life stage. In this study, we used data from a large, nationally representative German study (N = 16,132) to describe and explain age differences in loneliness from late adolescence to oldest old age. The age distribution of loneliness followed a complex nonlinear trajectory, with elevated loneliness levels among young adults and among the oldest old. The late-life increase in loneliness could be explained by lower income levels, higher prevalence of functional limitations, and higher proportion of singles in this age group. Consistent with an age-normative perspective, the association of income, relationship status, household size, and work status with loneliness differed between different age groups. In contrast, indicators of the quantity of social relationships (social engagement, number of friends, contact frequency) were universally associated with loneliness regardless of age. Overall, these findings show that sources of loneliness in older adults are well understood. Future research should focus on understanding the specific sources of loneliness in middle-aged adults. (PsycINFO Database Record
| S-EPMC8015413 | biostudies-literature
Project description:Some research suggests that compared with younger adults, older adults have more homogeneous, less diverse daily life experiences because everyday situations and activities become increasingly stable and routine. However, strong empirical tests of this assumption are scarce. In two complementary studies, we examined whether older age is associated with less diversity in daily life experiences (e.g., regarding social interaction partners, activities, and places across and within days) and, if so, to what extent health limitations account for these age differences. In Study 1, we used daily diaries to investigate diversity across days among younger (N = 246; Mage = 21.8 years, SD = 2.5) and older adults (N = 119; Mage = 67.7 years, SD = 5.3). In Study 2, we investigated diversity within days employing experience sampling methods over three weeks in an adult life span sample (N = 365; range = 14-88 years). Results showed that across and within days, the daily lives of older adults were less diverse regarding their social interaction partners. Yet, older adults reported more diversity in activities within days and across days in the afternoons, whereas younger adults reported less diverse activities partly due to working or studying more often. Age differences remained statistically significant when controlling for health limitations. We conclude that age differences in the diversity of daily life are nuanced, depending on the domain and the level of analysis. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
| S-EPMC8021140 | biostudies-literature
Project description:Prior research in non-U.S. samples has found a complex nonlinear relationship between loneliness and age. This research has shown that established predictors of loneliness - poor health, being unmarried, living alone, and having infrequent social interactions - help to explain age differences in loneliness. However, while some variables were found to be universal predictors of loneliness at all ages, others were relevant in specific age groups only. In this study, we describe age differences in frequency of loneliness from age 18 to 89+ years in the U.S., and examine age differences in predictors of loneliness from age-specificity and age-normative perspectives. We used cross-sectional nationally representative data from the General Social Survey (N = 2,477) and found a nonlinear relationship between age and loneliness that closely resembles prior research. However, we found no evidence for age-specific predictors of loneliness. Household income, household size, marital status, health, and frequency of socializing were "universal" predictors of loneliness; their associations with loneliness did not differ in strength with age. Our hypothesis that individuals who deviated from age-specific norms would experience more intense loneliness was not supported. Implications for research and loneliness interventions are discussed.
| S-EPMC8734589 | biostudies-literature
Project description:Promoting quality of life is a central theme in recent ageing policies, but what quality of life means in concrete terms for people in different stages of old age is rather unclear. This study presents a multi-dimensional model of care-related quality of life (crQoL) and, based on analyses of three Finnish cross-sectional datasets from the years 2004-2007, examines the distinctions between dimensions of QoL by age and gender, with a special focus on older home care clients. Correlation analyses (Pearson) and stepwise linear regression were applied to analyse variation in QoL by age group and the association between QoL and perceived quality of home care. The results suggest that individual QoL and the priorities of (physical, psychical, social, and environmental) dimensions in the assessment of QoL by older persons vary considerably and exhibit distinct profiles in different stages of ageing. In addition, four dimensions for good care corresponding to the crQoL model were identified and their empirical relevance demonstrated. From the perspective of older people in need of help, home care is not just about giving them the instrumental help they need to perform their daily activities, but rather about giving responsive care that reflects their personal preferences or their view on a "good life", and treats them with dignity and respect. The criteria for the evaluation of quality of home care should reflect these insights, and policy measures should take these differences into account.
| S-EPMC5547302 | biostudies-other
Project description:BackgroundMany factors can contribute to the exact makeup of the salivary microbiome. Differences in the oral microbiome occur with old age, which may be due to oral conditions and diseases associated with old age, such as edentulism, as well as other unknown causes.MethodsThe salivary microbiome was sampled in patients from a large urban clinic. For all subjects age, gender, periodontal status, caries status, presence of edentulism, medications, and tobacco usage were recorded. Multifactor analysis was used to study variation in salivary microbiome profiles linked to these factors.ResultsIn the population sampled, there were significantly higher numbers of edentulous subjects, and increased levels of polypharmacy found with aging. Large differences in alpha diversity and beta diversity of the salivary microbiome in the old age group were largely linked to edentulism. However, multivariable analysis revealed, even after adjusting for differences in edentulism, polypharmacy, tobacco usage, periodontal disease, caries level, and gender, that old age itself was associated with lower levels of taxa Porphyromonas endodontalis, Alloprevotella tannerae, Filifactor alocis, Treponema, Lautropia Mirabilis and Pseudopropionibacterium sp._HMT_194. Surprisingly, of these taxa, most were ones known to reside on or near tooth surfaces.ConclusionsAnother factor or factors beyond edentulism, polypharmacy and periodontal disease play a role in the differences seen in oral microbiome with old age. The nature of this factor(s) is not known.
| S-EPMC8489047 | biostudies-literature
Project description:In recent years, genome wide association studies have revolutionized the understanding of the genetic architecture of complex disease, particularly in the context of disorders that present in old age, such as type 2 diabetes and cardiovascular disease. This new era is made all the more compelling by the fact that, through extensive validation efforts, there is now very strong consensus among human geneticists on what the key loci are that contribute to the pathogenesis of these traits. However, as these variants have been almost exclusively uncovered in an adult setting, there is the question of when these genetic variants start exerting their effects; indeed many may start setting up an individual's predisposition to a disease of old age very early on in life. To this end, we review what breakthroughs have been made in elucidating which of these genetic factors are operating in childhood and conversely what discoveries have actually been made in the pediatric setting that have then been found subsequently to increase one's risk of a late-onset disease. After all, it well known that complex traits like obesity, type 2 diabetes and inflammatory bowel disease are strongly determined by genetic factors, but the isolation of genes in these complex phenotypes in adults has been impeded by interaction with strong environmental factors. Distillation of the genetic component in these complex traits, which will at least partially have origins in childhood, should be easier to determine in a pediatric setting, where the relatively short period of a child's lifetime limits the impact of environmental exposure.
| S-EPMC3501394 | biostudies-literature
Project description:Understanding how people of different ages decide in competition is a question of theoretical and practical importance. Using an experimental laboratory approach, this research investigates the ability of younger and older adults to think and act strategically with equal or unequal resources. In zero-sum games of resource allocation, younger adults (19-35 years) and older adults (65-81 years) made strategic decisions in competition against opponents of a similar age (Study 1; N = 120) or different age (Study 2; N = 120). The findings highlight people's ability to make good interpersonal decisions in complex scenarios: Both younger and older adults were aware of their relative strength (in terms of material resources) and allocated their resources adaptively. When competing against opponents of a similar age, people's gains were in line with game-theoretic predictions. However, younger adults made superior strategic allocations and won more frequently when competing against older adults. Measures of fluid cognitive and numerical abilities correlated with strategic behavior in interpersonal competition.
| S-EPMC8319396 | biostudies-literature