Age Patterns Research Articles

Development of a brief core set for knee dysfunction based on the International Classification of Functioning, Disability and Health: assessing construct validity and measurement potential

BackgroundThe comprehensive core set for knee dysfunction was developed to classify the functioning of people with any knee dysfunction. To be used as a clinical instrument to measure the functioning of people with knee dysfunction, the construct validity of the core set still needs to be assessed. The purpose of this study was to analyze the construct validity of the comprehensive core set for knee dysfunction as an instrument to measure functioning.MethodsA cross-sectional study with 200 participants with knee dysfunction with or without clinical diagnosis of knee pathology, with or without complaint of pain, with or without instability, and/or with or without knee movement restriction of any type. Participants were assessed using the comprehensive core set for knee dysfunction with 25 categories, the subjective form from the International Knee Documentation Committee scale, and measures of self-perceived general health and functioning. The construct validity of the core set was assessed by Rasch analysis, and the external construct validity was assessed by correlation between the score of the brief core set for knee dysfunction with the subjective form from the International Knee Documentation Committee scale, and scores of self-perception of health and functioning.ResultsTwelve categories were consistent with a unidimensional construct, with no difference in the response pattern for age, sex, educational level, and time of complaint. These categories were included in the brief core set for knee dysfunction. The mean score of the brief core set was 37 ± 21 points, a value classified as moderate impairment regarding functioning. Correlations with the subjective form from the International Knee Documentation Committee scale and scores of self-perception were adequate (p < 0.01; r > 0.5).ConclusionThe brief core set for knee dysfunction, a set with 12 categories, can be used as a clinical instrument to measure and score the functioning of people with knee dysfunction, aged between 18 and 89 years, with adequate construct validity.

Selection for early reproduction leads to accelerated aging and extensive metabolic remodeling in Drosophila melanogaster populations.

Experimental evolution studies that feature selection on life-history characters are a proven approach for studying the evolution of aging and variation in rates of senescence. Recently, the incorporation of genomic and transcriptomic approaches into this framework has led to the identification of hundreds of genes associated with different aging patterns. However, our understanding of the specific molecular mechanisms underlying these aging patterns remains limited. Here, we incorporated extensive metabolomic profiling into this framework to generate mechanistic insights into aging patterns in Drosophila melanogaster . Specifically, we characterized metabolomic change over time associated with accelerated aging in populations of D. melanogaster under selection for early reproduction compared to their controls. Using this data we: i) evaluated the evolutionary repeatability across the metabolome; ii) evaluated the value of the metabolome as a predictor of "biological age" in this system; and iii) identified specific metabolic pathways associated with accelerated aging. Generally, our findings suggest that the metabolome is a reliable predictor of age and senescence in populations that share a recent evolutionary history. Metabolomic analysis revealed that generations of selection for early reproduction resulted in highly repeatable alterations to the metabolome. Specifically, changes in carbohydrate, amino acid, and TCA cycle-related metabolite abundances over time point to metabolic remodeling that favors rapid early reproduction with long-term consequences for carbohydrate and protein utilization.

An Investigation into Diatomaceous Earth Stones: A New Tool in Paper Conservation

ABSTRACT This research explores the viability of using diatomaceous earth stone mats, a commercially manufactured, rigid, absorbent board marketed for home use (aka DE stones) as a sustainable tool in paper conservation. Analytical studies, including X-ray fluorescence, Fourier-transform infrared spectroscopy, gravimetry, colorimetry, accelerated aging, pH, solvent reactivity, and absorbency testing, were conducted at the National Archives and Records Administration on the DE stones and on Whatman® filter paper samples. The experiments with samples dried in direct contact with DE stones showed no undesirable transfer to the filter paper. Gravimetric analysis showed the drying rate of samples placed between DE stones was much more rapid than for samples placed between blotter or wool felt. Colorimetry before and after accelerated aging of samples dried in direct contact with DE stones showed no undesirable aging patterns. Successful case studies illustrate high potential for the use of DE stones in paper conservation treatments.

Aneuploidy rates and likelihood of obtaining a usable embryo for transfer among in vitro fertilization cycles using preimplantation genetic testing for monogenic disorders and aneuploidy compared with in vitro fertilization cycles using preimplantation genetic testing for aneuploidy alone

ObjectiveTo compare aneuploidy rates among IVF cycles using preimplantation genetic testing for monogenic disorders (PGT-M) and aneuploidy (PGT-A) compared to IVF cycles using PGT-A alone, and to determine the likelihood of obtaining at least one usable embryo in cycles using PGT-M+PGT-A compared with cycles using PGT-A alone. DesignRetrospective cohort study SubjectsAll IVF cycles for patients aged 18-45 undergoing PGT-A with or without concurrent PGT-M at a single genetics laboratory from November 2019 to March 2023. ExposureUse of PGT-M+PGT-A versus use of PGT-A alone Main Outcome MeasuresPer-cycle aneuploidy rate stratified by age, and per-cycle likelihood of obtaining at least one usable embryo stratified by age and inheritance pattern of monogenic disease ResultsA total of 72,522 IVF cycles were included; 4,255 cycles (5.9%) using PGT-M+PGT-A and 68,267 cycles (94.1%) using PGT-A alone. The PGT-M+PGT-A group was younger than the PGT-A alone group (<35 years old: 56.1% vs 30.5%, p<0.001). The majority of PGT-M cycles were performed for autosomal dominant pathogenic variants (42.4%), followed by autosomal recessive (36.5%), X-linked dominant (13.3%), and X-linked recessive (7.5%). The median number of embryos biopsied was higher in PGT-A alone compared to PGT-M+PGT-A cycles for patients aged <35, but it was equivalent in all other age groups. Age stratified aneuploidy rates did not significantly differ between PGT-M+PGT-A compared with PGT-A alone cycles. The probability of having a usable embryo declined with increasing age across all inheritance patterns. Compared with PGT-A alone, PGT-M+PGT-A cycles for patients aged ≤40 across all inheritance patterns were significantly less likely to yield a usable embryo (p<0.01), except in cycles for autosomal recessive diseases in the 38-40 age group and X-linked recessive diseases in the 35-37 age group. There were no consistent differences seen between groups in patients over 40. Cycles for patients with autosomal dominant diseases had the lowest likelihood of yielding a usable embryo for patients aged <43. ConclusionIVF cycles using PGT-M+PGT-A have similar age-specific aneuploidy rates to those using PGT-A alone. Cycles for patients ≤ 40 using PGT-M+PGT-A are significantly less likely to yield a usable embryo compared to those using PGT-A alone.

HANK Comes of Age

We study the aggregate and distributional effects of monetary policy in a heterogeneous agent New Keynesian model that explicitly represents the life cycle of households. The model matches the age patterns in the level and dispersion of labor income and financial wealth in the U.S. despite the absence of preference heterogeneity and portfolio adjustment costs. Monetary policy affects the consumption of young households mainly through labor income and the consumption of old households mainly through asset returns. More than half of the aggregate consumption response to an expansionary monetary policy shock comes from those below the age of 40. The shock redistributes welfare from the wealthiest old to the poorest young and increases average welfare of most cohorts.

Clinicopathological study of thyroid gland cancer among selected sample Basrah province between 2019-2022

Background. Thyroid cancer (TC) is the most prevalent cancer within the endocrine system and the head and neck region. Its incidence has been on the rise in Iraq over the past few decades, primarily owing to papillary thyroid carcinoma. This study’s objective is to explore the pathological variants, frequency, and demographic characteristics of TC in a sample of Basrah’s population and subsequently compare these elements with data from other regions in Iraq and globally. Methods. This study is a single-institutional retrospective review conducted at the Department of Pathology within Ports Teaching Hospital in Basrah, Iraq. We analyzed slides of thyroid tumors stained by Hematoxylin and Eosin (H&amp;E) and biometric data gathered from histopathological reports. The cases for this study were identified between 2019 and 2022. Results. In this study, 51 cases were examined, comprised of six males and 45 females. The average age and histopathology patterns were analyzed, finding that the most common type of TC was the classic form of papillary thyroid carcinoma, as seen in 16 cases. The study noted a predominant female presence, accounting for 88.2% of the cases, while males comprised 11.8%. The median age among all subjects was 38 years. Conclusions. A review of all slides featuring thyroid tumors stained with H&amp;E, combined with biometric data from histopathological reports, shows an increasing incidence of TC in Basrah City, Iraq. Predominantly, cases of papillary thyroid carcinoma outnumber those of follicular carcinoma.

Late Holocene vegetation dynamics: degree and regional patterns of the Dark Ages woodland regeneration (ad 300–700) in the Netherlands

AbstractDuring the Dark Ages, which include the Late Roman period (ad 270–450) and the Early Middle Ages (ad 450–1050), large-scale vegetation development in northwest Europe was characterised by widespread regeneration of woodlands. This regeneration phase represents a break from the extensive reduction in woodland from human activities in late Holocene vegetation history. In the Netherlands, possible causes for this reversal can be found in a decreased human impact on the landscape, a colder and possibly wetter climate, and geomorphological changes. This paper presents a synthesis from 38 pollen records from a range of sites across the Netherlands, from which regional differences in the degree of woodland regeneration and vegetation composition before and during the Dark Ages have been identified. Both original data as well as vegetation abundance modelled by REVEALS were used to assess the regrowth of the woodland cover. The observed trends were considered in terms of the landscape setting and population estimates in order to disentangle the relative importance of these forcing factors. The results indicate that landscape and human impact were the most important factors determining the vegetation structure and changes to it. The pollen data show that in the Netherlands, the clearance of woodland in the Roman period followed by its regrowth afterwards were greatest in the river area. This can be linked to a high population density there during the Roman period followed by a strong decrease of population in the Dark Ages and to increased flooding.

Differences between subjective and disability health expectancies across ages in older adults

Health expectancies (HEs) have become a key indicator for monitoring healthy aging. So far, they have mainly been calculated based on functional rather than subjective health measures. Yet, by integrating several dimensions (medical, social, and cultural), subjective health is also an important measure of an older person’s health status. In this study, we first estimated HEs using self-rated health (SRH), by age and sex. Second, we compared these results to those obtained when using a disability measure. We used pooled data from three prospective population-based cohorts including adults aged 65 years and over, living in Southwestern France (N = 4468). SRH was assessed using a single question and disability was measured using the Lawton scale. Healthy/Unhealthy Life Expectancies (HLE/UHLE) and Disability/Disability-Free Life Expectancies (DLE/DFLE) were estimated using the Interpolated Markov Chain program (IMaCh), separately in men and women. Women lived longer than men, with similar HLE but longer UHLE at all ages. The proportion of HLE in total LE decreased with age for both sexes and for women, it became smaller than the proportion of UHLE from age 73 onward. In both sexes, while the DLE was shorter than the UHLE in the youngest, a reversal was observed with advancing age. This change occurred earlier in women. Our study supports that SRH and disability showed different aging patterns, with sex and age differences. From a public health perspective, SRH and disability indicators appeared not interchangeable as they uncovered complementary but different information on the needs of aging people.

Middle to Late Ordovician flare‐up of granitoids, South Altyn Tagh: Reworking of exhumed continental crust

A flare‐up of granitoids occurred at 465–445 Ma in the South Altyn Tagh, synchronously with the exhumation of subducted continental crust. Nevertheless, it remains enigmatic whether a petrogenetic connection exists between them. Here, we report a 454–451 Ma monzogranite pluton, which is characterized by abundant inherited zircons, located in the northern margin of the South Altyn Tagh high‐pressure (HP)—ultrahigh‐pressure (UHP) metamorphic terrane. U–Pb ages and Hf–O isotopic compositions of inherited and synmagmatic zircons are investigated to trace the source rocks and petrogenesis of this pluton. The inherited zircons (zircons that predate the magmatism) exhibit a wide range of ages from 2618 to 484 Ma, displaying three major peaks at 1800–1100 Ma, 1000–800 Ma and 500 Ma. By comparing these inheritance age patterns with zircon spectra of main (meta‐)sedimentary sequences and the widespread Early Neoproterozoic granites (presently as granitic gneisses) in South Altyn Tagh, along with zircon εHf(t) and whole‐rock Nd isotopic composition, we argue that the main source rocks of the studied monzogranite are Early Neoproterozoic granitic gneisses and Late Mesoproterozoic paragneisses from the South Altyn Tagh HP–UHP metamorphic terrane. The ca. 500 Ma inherited zircons have a metamorphic origin, which is simultaneous with the peak metamorphic ages of HP–UHP metamorphic rocks in the Altyn Tagh Complex. These observations indicate that the source rocks of the monzogranite pluton are the subducted continental crust, which underwent metamorphism at ca. 500 Ma and followed by partial melting at 454–451 Ma. In addition, synmagmatic zircons exhibit variable δ18O and εHf(t) values ranging from 5.4 to 11.7‰ and from −19 to +10.3, respectively, indicating a minor contribution of mantle‐derived melts in the formation of the monzogranite. Given the studied pluton and contemporaneous extensive granitoids (465–445 Ma), characterized by similar geochemistry and source rocks, are synchronous with the final exhumation of subducted South Altyn Tagh continental crust, we propose that the reworking of exhumed continental crust at middle to lower crustal depths is their main petrogenesis.

Population clustering of structural brain aging and its association with brain development.

Structural brain aging has demonstrated strong inter-individual heterogeneity and mirroring patterns with brain development. However, due to the lack of large-scale longitudinal neuroimaging studies, most of the existing research focused on the cross-sectional changes of brain aging. In this investigation, we present a data-driven approach that incorporate both cross-sectional changes and longitudinal trajectories of structural brain aging and identified two brain aging patterns among 37,013 healthy participants from UK Biobank. Participants with accelerated brain aging also demonstrated accelerated biological aging, cognitive decline and increased genetic susceptibilities to major neuropsychiatric disorders. Further, by integrating longitudinal neuroimaging studies from a multi-center adolescent cohort, we validated the "last in, first out" mirroring hypothesis and identified brain regions with manifested mirroring patterns between brain aging and brain development. Genomic analyses revealed risk loci and genes contributing to accelerated brain aging and delayed brain development, providing molecular basis for elucidating the biological mechanisms underlying brain aging and related disorders.

Underneath the Sheets: a Cross-Cultural Cluster Analysis of Older Adults’ Patterns of Aging and Sexual Well-Being in Portugal and Mexico

AbstractThis study aims to assess the patterns of life satisfaction with life (SwL), sexual satisfaction, and adjustment to aging (AtA), of older adults in Mexico and Portugal. A sample of 658 older adults, aged 65 years-old and older, from Mexico and Portugal were recruited for this cross-cultural study. The following measures were applied: (a) Adjustment to Aging Scale (ATAS); (b) Satisfaction with Life Scale (SwLS); (c) New Sexual Satisfaction Scale (NSSS); (d) Mini-Mental State Exam; and (e) Sociodemographic, health and lifestyle questionnaire. Clusters were identified and characterized by using K-means cluster analysis, encompassing SwL, AtA, and sexual satisfaction. Sexual well-being differences among clusters were analyzed with One-way ANOVAs. Findings indicated three clusters, which explained 76.4% (R-sq = 0.764) of the total variance: Cluster #1: “Moderately adjusted older adults” (n = 355, 53.9%), Cluster #2: “Moderately fulfilled older adults” (n = 265, 40.3%), and Cluster 3: “Well adjusted and satisfied older adults” (n = 38, 5.8%). Participants in Cluster #1 were mostly Mexican, with moderate levels of AtA and reduced sexual satisfaction and SwL. Conversely, Cluster #2 predominantly consisted of Portuguese participants with moderate sexual satisfaction and SwL, and lower levels of AtA. Participants from Cluster #3 were mostly Portuguese with high levels of AtA, sexual satisfaction, and SwL. This innovative study explored the intricate relationship between sexual well-being, the ability to adjust to aging, and overall SwL, in two different cultural contexts. Findings contributed to the understanding of the relationship between these three variables and for developing tailored future interventions and service planning with older adults in different cultures.

National, regional, and global trends in insufficient physical activity among adults from 2000 to 2022: a pooled analysis of 507 population-based surveys with 5·7 million participants

Insufficient physical activity increases the risk of non-communicable diseases, poor physical and cognitive function, weight gain, and mental ill-health. Global prevalence of adult insufficient physical activity was last published for 2016, with limited trend data. We aimed to estimate the prevalence of insufficient physical activity for 197 countries and territories, from 2000 to 2022. We collated physical activity reported by adults (aged ≥18 years) in population-based surveys. Insufficient physical activity was defined as not doing 150 minutes of moderate-intensity activity, 75 minutes of vigorous-intensity activity, or an equivalent combination per week. We used a Bayesian hierarchical model to compute estimates of insufficient physical activity by country or territory, year, age, and sex. We assessed whether countries or territories, regions, and the world would meet the global target of a 15% relative reduction of the prevalence of insufficient physical activity by 2030 if 2010-22 trends continue. We included 507 surveys across 163 countries and territories. The global age-standardised prevalence of insufficient physical activity was 31·3% (95% uncertainty interval 28·6-34·0) in 2022, an increase from 23·4% (21·1-26·0) in 2000 and 26·4% (24·8-27·9) in 2010. Prevalence was increasing in 103 (52%) of 197 countries and territories and six (67%) of nine regions, and was declining in the remainder. Prevalence was 5 percentage points higher among female (33·8% [29·9-37·7]) than male (28·7% [25·0-32·6]) individuals. Insufficient physical activity increased in people aged 60 years and older in all regions and both sexes, but age patterns differed for those younger than 60 years. If 2010-22 trends continue, the global target of a 15% relative reduction between 2010 and 2030 will not be met (posterior probability <0·01); however, two regions, Oceania and sub-Saharan Africa, were on track with considerable uncertainty (posterior probabilities 0·70-0·74). Concerted multi-sectoral efforts to reduce insufficient physical activity levels are needed to meet the 2030 target. Physical activity promotion should not exacerbate sex, age, or geographical inequalities. Ministry of Public Health, Qatar, and World Health Organization. For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Transcriptome analysis of cynomolgus macaques throughout their lifespan reveals age-related immune patterns

Despite the different perspectives by diverse research sectors spanning several decades, aging research remains uncharted territory for human beings. Therefore, we investigated the transcriptomic characteristics of eight male healthy cynomolgus macaques, and the annual sampling was designed with two individuals in four age groups. As a laboratory animal, the macaques were meticulously shielded from all environmental factors except aging. The results showed recent findings of certain immune response and the age-associated network of primate immunity. Three important aging patterns were identified and each gene clusters represented a different immune response. The increased expression pattern was predominantly associated with innate immune cells, such as Neutrophils and NK cells, causing chronic inflammation with aging whereas the other two decreased patterns were associated with adaptive immunity, especially “B cell activation” affecting antibody diversity of aging. Furthermore, the hub gene network of the patterns reflected transcriptomic age and correlated with human illness status, aiding in future human disease prediction. Our macaque transcriptome profiling results offer systematic insights into the age-related immunological features of primates.

Age-related physiological dysregulation progresses slowly in semi-free-ranging chimpanzees.

Lifestyle has widespread effects on human health and aging. Prior results from chimpanzees (Pan troglodytes), one of humans' closest evolutionary relatives, indicate that these lifestyle effects may also be shared with other species, as semi-free-ranging chimpanzees fed a naturalistic diet show healthier values in several specific health biomarkers, compared with their sedentary, captive counterparts. Here, we examined how lifestyle factors associated with different environments affect rates of physiological aging in closely related chimpanzees. We compared physiological dysregulation, an index of biological aging, in semi-free-ranging chimpanzees in an African sanctuary versus captive chimpanzees in US laboratories. If the rate of aging is accelerated by high-calorie diet and sedentism, we predicted greater age-related dysregulation in the laboratory populations. Conversely, if costs of a wild lifestyle accelerate aging, then semi-free-ranging chimpanzees at the sanctuary, whose environment better approximates the wild, should show greater age-related dysregulation. We further tested whether dysregulation differed based on sex or body system, as in humans. We found that semi-free-ranging chimpanzees showed lower overall dysregulation, as well as lower age-related change in dysregulation, than laboratory chimpanzees. Males experienced lower dysregulation than females in both contexts, and the two populations exhibited distinct aging patterns based on body system. Our results support the conclusion that naturalistic living conditions result in healthier aging in chimpanzees. These data provide support for the proposal that lifestyle effects on human health and aging are conserved from deeper into our evolutionary history.

DNA Damage and Senescence in the Aging and Alzheimer's Disease Cortex Are Not Uniformly Distributed.

Alzheimer's disease (AD) is a neurodegenerative illness with a typical age of onset exceeding 65 years of age. The age dependency of the condition led us to track the appearance of DNA damage in the frontal cortex of individuals who died with a diagnosis of AD. The focus on DNA damage was motivated by evidence that increasing levels of irreparable DNA damage are a major driver of the aging process. The connection between aging and the loss of genomic integrity is compelling because DNA damage has also been identified as a possible cause of cellular senescence. The number of senescent cells has been reported to increase with age, and their senescence-associated secreted products are likely contributing factors to age-related illnesses. We tracked DNA damage with 53BP1 and cellular senescence with p16 immunostaining of human post-mortem brain samples. We found that DNA damage was significantly increased in the BA9 region of the AD cortex compared with the same region in unaffected controls (UCs). In the AD but not UC cases, the density of cells with DNA damage increased with distance from the pia mater up to approximately layer V and then decreased in deeper areas. This pattern of DNA damage was overlaid with the pattern of cellular senescence, which also increased with cortical depth. On a cell-by-cell basis, we found that the intensities of the two markers were tightly linked in the AD but not the UC brain. To test whether DNA damage was a causal factor in the emergence of the senescence program, we used etoposide treatment to damage the DNA of cultured mouse primary neurons. While DNA damage increased after treatment, after 24 h, no change in the expression of senescence-associated markers was observed. Our work suggests that DNA damage and cellular senescence are both increased in the AD brain and increasingly coupled. We propose that in vivo, the relationship between the two age-related processes is more complex than previously thought.

Patterns of cognitive domain abnormalities enhance discrimination of dementia risk prediction: The ARIC study.

The contribution of neuropsychological assessments to risk assessment for incident dementia is underappreciated. We analyzed neuropsychological testing results in dementia-free participants in the Atherosclerosis Risk in Communities (ARIC) study. We examined associations of index domain-specific neuropsychological test performance with incident dementia using cumulative incidence curves and Cox proportional hazards models. Among 5296 initially dementia-free participants (mean [standard deviation] age of 75.8 [5.1] years; 60.1% women, 22.2% Black) over a median follow-up of 7.9 years, the covariate-adjusted hazard ratio varied substantially depending on the pattern of domain-specific performance and age, in an orderly manner from single domain language abnormalities (lowest risk) to single domain executive or memory abnormalities, to multidomain abnormalities including memory (highest risk). By identifying normatively defined cognitive abnormalities by domains based on neuropsychological test performance, there is a conceptually orderly and age-sensitive spectrum of risk for incident dementia that provides valuable information about the likelihood of progression. Domain-specific cognitive profiles carry enhanced prognostic value compared to mild cognitive impairment. Single-domain non-amnestic cognitive abnormalities have the most favorable prognosis. Multidomain amnestic abnormalities have the greatest risk for incident dementia. Patterns of domain-specific risks are similar by sex and race.

The age pattern of the gender gap in mortality: stylized evidence across COVID-19 pandemic times

The age pattern of the gender gap in mortality: stylized evidence across COVID-19 pandemic times

Age-Related Decline in Blood-Brain Barrier Function is More Pronounced in Males than Females in Parietal and Temporal Regions.

The blood-brain barrier (BBB) serves as a critical protection mechanism for the CNS. A natural decline of BBB function with aging has been reported in both animal and human studies, with possible differences in BBB function by sex. Using our MRI technique, DP-pCASL that measures water exchange rate (kw) without contrast in 186 participants from diverse race and age groups, we identified age and sex-specific patterns in BBB kw especially in parietal and temporal regions. We observed of a decline in kw beginning in the early 60s, especially in males. Our study unveils the dynamic spatiotemporal pattern of kw differences with age and sex, which serve as a foundation for understanding aberrations of BBB function in neurodegenerative and other brain disorders.

Integration of white mica in situ 87Rb/87Sr with in situ and step-heat 40Ar/39Ar dates in orogenic settings

White mica is common in continental rocks, and often (de)forms in response to structural and metamorphic processes in orogenic settings. It has been most typically dated via step heat or in situ 40Ar/39Ar methods. However, with in situ 87Rb/87Sr geochronology now possible via in line mass-chemical-mass filtering of Rb and Sr isotopes in tandem mass spectrometers, the contrasting accumulation of radiogenic Ar vs. Sr in white mica under deformation and metamorphism should allow for more nuanced and improved interpretations of the geological evolution of white mica. Here, we apply the in situ 87Rb/87Sr dating method to white mica previously dated with the in situ and step heat 40Ar/39Ar methods in three case studies with contrasting structural and metamorphic histories. The results of these comparative studies are used to propose a framework for interpreting paired white mica 40Ar/39Ar and 87Rb/87Sr datasets. In general, white mica 87Rb/87Sr ages are expected to be equivalent to 40Ar/39Ar ages under conditions of low temperature metamorphic, fluid-mediated, or dynamic (re-) crystallization. Under high temperature conditions of igneous or metamorphic white mica (re-)crystallization, 87Rb/87Sr ages are more likely to represent the (re-)crystallization event, with 40Ar/39Ar ages representing post-crystallization cooling. Deformation and/or dynamic (re-)crystallization of white mica can produce complex, spatially controlled age patterns for both chronometers, requiring more nuanced interpretations. These results and framework point to the value of combining both chronometers in orogenic studies to reduce uncertainties in interpretation and test assumptions in dating metamorphic and deformation processes in orogens.

DNA Methylation Demonstrates Bronchoalveolar Cell Senescence in People Living with HIV: An Observational Cohort Study.

DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. We investigated whether bronchoalveolar lavage (BAL) cells of people living with HIV (PLWH) demonstrate epigenetic disruptions and advanced epigenetic aging. BAL cell DNA methylation from 25 PLWH and 16 HIV-uninfected individuals were tested for differential methylation of Alu and LINE-1 sites, markers of aging. We used a weighted gene correlation network analysis to identify HIV- and age-associated co-methylation networks. We tested the effect of HIV on DNA methylation using a robust linear model (false discovery rate < 0.10). The BAL cells of PLWH were marked by global hypomethylation in both Alu and LINE-1 elements. Six co-methylated CpG networks were identified that were significantly associated with age; of these, the red module was significantly differentially methylated in PLWH and enriched pathways (e.g., Ras signaling and T-cell receptors). We identified 6428 CpG sites associated with HIV. We have shown here for the first time that alterations in the DNA methylation of BAL cells in the lung with HIV show a pattern of advanced aging. This study strongly supports that HIV may contribute to an increased the risk of lung comorbidities through the epigenetics of aging.