Anti-age Cosmetology in Older Age and Aging Scenarios of Russian Women in the Perspective of the Life Course

Editor's Spotlight/Take 5: Patients Older Than 40 Years With Unilateral Occupational Claims for New Shoulder and Knee Symptoms Have Bilateral MRI Changes.

The aged cardiovascular risk patient

Summary 1 Classical evolutionary theory states that senescence should arise as a consequence of the declining force of selection late in life. Although the quantitative genetic predictions of hypotheses derived from this theory have been extensively tested in laboratory studies of invertebrate systems, relatively little is known about the genetics of ageing in the wild. 2 Data from long-term ecological studies is increasingly allowing quantitative genetic approaches to be used in studies of senescence in free-living populations of vertebrates. We review work to date and argue that the patterns are broadly consistent with theoretical predictions, although there is also a clear need for more empirical work. 3 We argue that further advances in this field of research might be facilitated by increased use of reaction norm models, and a decreased emphasis on attempting to discriminate between mutation accumulation and antagonistic pleiotropy models of senescence. We also suggest a framework for the better integration of environmental and genetic effects on ageing. 4 Finally, we discuss some of the difficulties in applying quantitative genetic models to studies of senescence outside the laboratory. In particular we highlight the problems that viability selection can cause for an accurate estimation of parameters used in the prediction of age-trajectory evolution.

People living with HIV (PLWH) are aging but are often excluded from clinical studies because of pragmatical and ethical concerns. Therefore, the effect of aging on the pharmacokinetics and drug-drug interaction (DDI) magnitudes of antiretroviral drugs remain uncertain. Consequently, clinical guidance regarding dose adjustment for antiretroviral drugs and the clinical management of DDIs with advanced aging are missing. Studies presented in this thesis combined clinically observed data with physiologically based pharmacokinetic (PBPK) modelling to investigate the continuous effect of aging on drug pharmacokinetics and DDI magnitudes. The PBPK model was developed in the mathematical programming language Matlab®. A virtual population considering age-related changes in demographics, physiology, and biology informed the model. Clinically observed data of ten non-HIV drugs being commonly administered as comedications to aging PLWH were used to verify the predictive power of the PBPK model to simulate drug disposition in the elderly. Extrapolating the pharmacokinetics of all investigated ten drugs across adulthood (20 to 99 years) elucidated that the progressively decreasing drug clearance drove age-related pharmacokinetic changes, which itself was caused by the decline of the hepatic and renal blood flow and the glomerular filtration rate. Age-dependent pharmacokinetic alterations were independent of drug characteristics. Additional clinical data of 52 drugs obtained from young and elderly individuals verified this general model-based hypothesis. Concentration-time profiles of ten antiretroviral drugs, belonging to the current first-line treatment, were obtained in two clinical studies including PLWH at least 55 years, who participated in the Swiss HIV Cohort Study. These clinically observed data were generally predicted within the 95% confidence interval of the PBPK model, demonstrating the ability of the used approach to predict real-life plasma concentrations from PLWH, who had a declined kidney function (e.g. the glomerular filtration rate was 65.6 ± 19.2 mL/min/1.73m²) and common comorbidities (e.g. hypertension). Age-related pharmacokinetic changes of antiretroviral drugs across adulthood were found to be similar to non-HIV drugs, indicating a marginal increase in antiretroviral drug exposure with advanced aging. One of the conducted clinical studies in PLWH at least 55 years was designed to investigate DDI magnitudes between amlodipine, atorvastatin, or rosuvastatin and a dolutegravir (no interaction expected) or a boosted darunavir (high interaction potential) containing antiretroviral regimen. The comparison with historical data obtained in young PLWH aged 20 to 50 years yielded no changes in the DDI magnitudes between both investigated age groups. These clinically observed data were used to verify DDI simulations of the developed PBPK framework in the elderly and subsequently DDI magnitudes were predicted across the entire adult lifespan. The model indicated that DDI magnitudes were unchanged across adulthood regardless of the involved drugs, the DDI mechanism, or the sex of the investigated individual. This general model-based hypothesis was verified with independent clinically observed data from 17 DDIs. As DDI magnitudes are not impacted by aging, static methods can be applied to predict DDI magnitudes in elderly patients, who receive two drugs with an uncharacterized DDI magnitude. Predictions are based on the fraction of metabolism by a specific enzyme and the strength of an inhibitor or inducer. In contrast to the PBPK approach, the static method provides a more straightforward supportive tool to rationalize dose adjustments to overcome a given DDI. In conclusion, this thesis demonstrates marginal pharmacokinetic alterations of antiretroviral drugs and no age-related changes of DDI magnitudes. Therefore, a dose adjustment of antiretroviral drugs or a different management of DDIs in clinical practice are a priori not necessary when treating aging male and female PLWH in the absence of severe comorbidities. These general rules being broadly applicable to antiretroviral and non-HIV drugs support the overall care of elderly PLWH beyond HIV and therapies of future effective drugs.

Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?

A persistent misperception: assisted reproductive technology can reverse the “aged biological clock”

Age-related changes in histone modification in rat gastrocnemius muscle.

The results of extensive human and animal studies suggest that declining food intake and body weight observed in the later stages of life may be part of the normal progression of physiological decline observed during aging. Proposed etiologies cover a wide range of biological and psychological conditions. Studies in humans suggest an imbalance in homeostatic mechanisms governing hunger and satiety. That is, while older vs. younger individuals retain a similar drive (hunger) to eat, satiety occurs sooner during a meal in aged people and leads to an overall decrease in daily food intake. Age-related weight loss and a reduction in food intake have also been observed in laboratory animals. Alterations in neurochemical control of energy balance, especially as they relate to long-term regulation of food intake, have received much attention in recent years as the likely mechanism underlying age-related spontaneous weight loss. Age-related changes to neuroendocrine factors such as neuropeptide Y, GABA, CCK, leptin, and insulin have been linked to spontaneous weight loss observed during late life. This brief review provides an update on putative mechanisms underlying the dysregulation of feeding during advanced age that result in body weight loss.

The microstructural architecture of white matter supporting information flow across local circuits and large-scale networks changes throughout the lifespan. However, the genetic and cellular factors underlying age-related variations in white matter microstructure have yet to be established. Here, we examined the genetic associates of individual differences in diffusion-based measures of white matter in a population-based cohort (N=29,862) from the UK Biobank. Estimates of heritability from Genome-Wide Association Study (GWAS) data revealed that genetic factors are linked to population variability in 96.1% of 432 tract microstructural measures. The presence of shared genetic influences was observed to be greater within, relative to between, broad tract classes (commissural, association, projection, and complex cerebellar). Age associations with microstructural changes were estimated across diffusivity measures, with association class tracts showing the greatest vulnerability to age-related decline in older adults. Analyses of imputed cellular associates of age-related changes in white matter revealed a preferential relationship with cell gene markers of oligodendrocytes and other glial cell types, with sparse relationships observed for inhibitory and excitatory cells. These data indicate that white matter tract microstructure is shaped by genetic factors and suggest a role for glial cell-related transcripts in late-life changes in the structural wiring properties of the human brain.

Presbyopia is an age-related ocular disorder where accommodative ability declines so that an individual's focusing range is insufficient to provide visual clarity for near and distance vision tasks without corrective measures. With age, the eye exhibits changes in biomechanical properties of many components involved in accommodation, including the lens, sclera, and ciliary muscle. Changes occur at different rates, affecting accommodative biomechanics differently, but individual contributions to presbyopia are unknown. We used a finite element model (FEM) of the accommodative mechanism to simulate age-related changes in lens stiffness, scleral stiffness, and ciliary contraction to predict differences in accommodative function. The FEM predicts how ciliary muscle action leads to lens displacement by initializing a tensioned unaccommodated lens (Phase 0) then simulating ciliary muscle contraction in accommodation (Phase 1). Model inputs were calibrated to replicate experimentally measured lens and ciliary muscle in 30-year-old eyes. Predictions of accommodative lens deformation were verified with additional imaging studies. Model variations were created with altered lens component stiffnesses, scleral stiffness, or ciliary muscle section activations, representing fifteen-year incremental age-related changes. Model variations predict significant changes in accommodative function with age-related biomechanical property changes. Lens changes only significantly altered lens thickening with advanced age (46% decrease at 75 years old) while sclera changes produced progressive dysfunction with increasing age (23%, 36%, 49% decrease at 45, 60, and 75 years old). Ciliary muscle changes effected lens position modulation. Model predictions identified potential mechanisms of presbyopia that likely work in combination to reduce accommodative function and could indicate effectiveness of treatment strategies and their dependency on patient age or relative ocular mechanical properties.

Are body fat and inflammatory markers independently associated with age-related muscle changes?

The population is ageing. Globally, the number of older adults (aged 60 years or over) is expected to more than double, from 841 million people in 2013 to more than 2 billion in 2050. 1 In light of the increasing size of the older adult population, there is a pressing need to better identify the nature of, and mechanisms underlying, age-related vision impairment and the functional impact it has on the performance of everyday activities in older adults. The content of this feature issue reflects the diversity of research currently being undertaken on the topic of the ageing visual system and the important visual challenges that this presents for our ageing patient population. The scope is broad and includes topics relating to three main related themes: 1) The treatment of age-related ocular disorders and diseases and their consequences, including presbyopia and AMD; 2) The impact of age-related visual changes on everyday activities in older people, including mobility, driving and falls; and 3) The interaction of age-related visual impairments and other age-related impairments including hearing and cognitive changes. Four papers focus on theme 1, which relates to the treatment of age-related ocular disorders and diseases, of which three are reviews of relevant topics. Charman 2 summarises current surgical approaches for the correction of the perennial problem of presbyopia and reports that while there is a significant amount of activity in this area, there is no surgical silver bullet currently available. Evans and Lawrenson 3 in their review of dietary interventions for the prevention or slowing of AMD progression, find no high quality evidence suggesting nutritional supplementation is beneficial for the prevention of AMD, with some limited evidence that those with AMD may benefit from supplementation. Adaptive strategies such as eccentric viewing for AMD have also been advocated, however, Gaffney et al. 4 fail to find conclusive

The nail unit is an important part of cosmetic appearance of an individual. Older people are at an increased risk of nail alterations, including normal age-related changes and disorders that more commonly affect this specific population. To identify and evaluate the age-related nail changes and disorders in Egyptian elderly people both clinically and histopathologically. A total of 400 adult subjects, not complaining from any dermatological disease, were included in the present study; half of them were elderly of 60years and above (elderly group). Meanwhile, the other half served as a control group with younger ages. Full history taking, general and local examinations as well as nail biopsies were performed from selected cases with age-related nail changes and disorders. Nail changes were significantly (P<0.05) more common in old age group (88%) compared to control subjects (39%). The commonest age-related nail changes noticed were pale, dull, opaque, and lusterless nails (73%); brittle nails (67.5%); decreased lunula visibility (49%); and onychorrhexis (45.5%). They showed highly significant increase (P<0.001) when compared with control group. The prevalence of nail changes and disorders has increased among elderly patients although they are frequently overlooked by health care providers. Dermatologist should be aware about various nail changes related to aging and those associated with other dermatoses or systemic diseases. Histopathologic picture can enhance the accuracy of clinical diagnosis of various nail changes and disorders.

Approach to acute psychosis in older adults.

Beyond the tip of the iceberg: Health literacy in older people.