BACKGROUND: Multiple epidemiological studies have observed the connection between aging and brain volumes. The concept of accelerated biological aging (BA) is more powerful for observing the degree of aging of an individual than chronologic age (CA). The objective of this study is to explore the relationship between BA and brain volumes.
METHODS: BA was measured from clinical traits using two blood-chemistry algorithms, the Klemera-Doubal method (KDM) and the PhenoAge. The two age acceleration biomarkers were calculated by the residuals from regressing CA, termed \"KDM-acceleration\" and \"PhenoAge-acceleration\". Brain volumes were from brain magnetic resonance imaging (MRI) data. After adjustment for confounding factors, general linear regression models were used to examine associations between KDM-acceleration and PhenoAge-acceleration and brain volumes, respectively. Additionally, we stratified participants by sex, age, and the four quartiles of the Townsend Deprivation Index (TDI) for extra subgroup analysis.
RESULTS: 14,725 participants with available information were enrolled. After full adjustment, we observed negative associations between KDM-acceleration and brain volumes, such as gray matter (β = -0.029), white matter (β = -0.021), gray and white matter (β = -0.026), and hippocampus (β = -0.011 for left and β = -0.014 for right). There were also negative associations between PhenoAge-acceleration and brain volumes, such as white matter (β = -0.008), gray and white matter (β = -0.010), thalamus (β = -0.012 for left and β = -0.012 for right). In the subgroup analysis stratified by sex, age, and the four quartiles of TDI, the association between KDM-acceleration and PhenoAge-acceleration and brain volumes still existed. In subgroup analyses, the variation in associations suggests that socioeconomic and biological factors may differentially influence brain aging.
CONCLUSIONS: Our research indicated that more advanced BA was associated with less brain tissue.

BACKGROUND: Individuals with bipolar disorders (BD) have an estimated loss of life expectancy around 10-15 years. Several laboratory-measured biomarkers of accelerated aging exist (e.g., telomere length), however with a questionable transferability to bedside. There is a need for easily and inexpensively measurable markers of aging, usable in routine practice, such as BioAge.
METHODS: We calculated BioAge that estimates biological age based on routine blood tests and a physical exam, in a sample of 2220 outpatients with BD. We investigated associations between BioAge Acceleration (BioAgeAccel), which is an indicator of accelerated aging, and sociodemographic variables, clinical variables, and current psychotropic medication use.
RESULTS: Mean chronological age was 40.2 (±12.9). Mean BioAge was 39.1 (±12.4). Mean BioAgeAccel was 0.08 (±1.8). A minority of individuals (15%) had a BioAgeAccel above 2 years. Multivariable analyses suggested strong associations between a higher BioAgeAccel and younger age, male sex, overweight and sleep disturbances. Regarding current psychotropic medication use, discrepancies between univariate and multivariate analyses were observed.
CONCLUSIONS: A minority of individuals with BD had an accelerated aging as measured by BioAge. We identified associations with potentially modifiable factors, such as higher body mass index and sleep disturbances, that are however nonspecific to BD. These results require replications in independent samples of individuals with BD, and comparisons with a control group matched for age and gender. Longitudinal studies are also required to test whether any change in metabolic health, or sleep might decrease BioAgeAccel.

OBJECTIVE: To validate AnthropoAge, a new metric of biological age (BA), for prediction of all-cause mortality and age-related outcomes and characterize population-specific aging patterns using multinational longitudinal cohorts.
METHODS: We analyzed harmonized multinational data from the Gateway to Global Aging, including studies from the US, England, Mexico, Costa Rica, and China. We used body mass index and waist-to-height ratio to estimate AnthropoAge and AnthropoAgeAccel in participants aged 50-90 years old as proxies of BA and age acceleration, respectively. We compared the predictive capacity for all-cause mortality of AnthropoAge and chronological age (CA) using Cox models, described aging trends in all countries and explored the utility of longitudinal assessments of AnthropoAgeAccel to predict new-onset functional decline and age-related diseases using generalized estimating equations (GEE).
RESULTS: Using data from 55,628 participants, we found AnthropoAge (c-statistic 0.772) outperformed CA (0.76) for prediction of mortality independently of comorbidities, sex, race/ethnicity, education, and lifestyle; this result was replicated in most countries individually except for Mexico. Individuals with accelerated aging had a ~39% higher risk of death, and AnthropoAge also identified trends of faster biological aging per year. In longitudinal analyses, higher AnthropoAgeAccel values were independently predictive of self-reported health deterioration and new-onset deficits in basic/instrumental activities of daily living (ADL/IADL), diabetes, hypertension, cancer, chronic lung disease, myocardial infarction, and stroke.
CONCLUSIONS: AnthropoAge is a robust and reproducible BA metric associated with age-related outcomes. Its implementation could facilitate modeling trends of biological aging acceleration in different populations, although recalibration may enhance its utility in underrepresented populations such as individuals from Latin America.

UNASSIGNED: Chronological age (CAge), biological age (BAge), and accelerated age (AAge) are all important for aging-related diseases. CAge is a known risk factor for benign prostatic hyperplasia (BPH); However, the evidence of association of BAge and AAge with BPH is limited. This study aimed to evaluate the association of CAge, Bage, and AAge with BPH in a large prospective cohort.
UNASSIGNED: A total of 135,933 males without BPH at enrolment were extracted from the UK biobank. We calculated three BAge measures (Klemera-Doubal method, KDM; PhenoAge; homeostatic dysregulation, HD) based on 16 biomarkers. Additionally, we calculated KDM-BAge and PhenoAge-BAge measures based on the Levine method. The KDM-AAge and PhenoAge-AAge were assessed by the difference between CAge and BAge and were standardized (mean = 0 and standard deviation [SD] = 1). Cox proportional hazard models were applied to assess the associations of CAge, Bage, and AAge with incident BPH risk.
UNASSIGNED: During a median follow-up of 13.150 years, 11,811 (8.690%) incident BPH were identified. Advanced CAge and BAge measures were associated with an increased risk of BPH, showing threshold effects at a later age (all P for nonlinearity <0.001). Nonlinear relationships between AAge measures and risk of BPH were also found for KDM-AAge (P = 0.041) and PhenoAge-AAge (P = 0.020). Compared to the balance comparison group (-1 SD < AAge < 1 SD), the accelerated aging group (AAge > 2 SD) had a significantly elevated BPH risk with hazard ratio (HR) of 1.115 (95% CI, 1.000-1.223) for KDM-AAge and 1.180 (95% CI, 1.068-1.303) for PhenoAge-AAge, respectively. For PhenoAge-AAge, subgroup analysis of the accelerated aging group showed an increased HR of 1.904 (95% CI, 1.374-2.639) in males with CAge <50 years and 1.233 (95% CI, 1.088-1.397) in those having testosterone levels <12 nmol/L. Moreover, AAge-associated risk of BPH was independent of and additive to genetic risk.
UNASSIGNED: Biological aging is an independent and modifiable risk factor for BPH. We suggest performing active health interventions to slow biological aging, which will help mitigate the progression of prostate aging and further reduce the burden of BPH.

The association between cardiometabolic risk factors and cognitive function has been well documented, but the underlying mechanisms are not fully understood. This longitudinal study aimed to investigate the potential mediating role of DNA methylation in this association. We conducted the analyses in 3 708 participants (mean [standard deviation {SD}] age: 67.3 [9.5], women: 57.9%) from the Health and Retirement Study who were assessed in the 2014-2020 waves, had Infinium Methylation EPIC BeadChip methylation assays from the 2016 Venous Blood Study, and had cognitive assessment between 2016 and 2020. Causal mediation analyses were used to test the mediation role of DNA methylation in the associations between cardiometabolic risk factors and cognition, adjusting for demographic, socioeconomic, and lifestyle factors. Hypertension (-0.061 in composite cognitive z-score; 95% confidence interval [CI: -0.119, -0.004]) and diabetes (-0.134; 95% CI: [-0.198, -0.071]) were significantly associated with worse cognitive function while abnormal body weight and hypercholesterolemia were not. An increased number of cardiometabolic risk factors was associated with worse cognitive function (p = .002). DNA methylation significantly mediated the association of hypertension (mediated effect on composite cognitive z-score: -0.023; 95% CI: -0.033, -0.014), diabetes (-0.022; 95% CI: -0.032, -0.014), and obesity (-0.021; 95% CI: -0.033, -0.011) with cognitive function, whereas the mediation effect was not observed for having hypercholesterolemia. The estimated proportions mediated were 37.4% for hypertension and 16.7% for diabetes. DNA methylation may be an important mediator linking cardiometabolic risk factors to worse cognition and might even provide a potential target for dementia prevention.

BACKGROUND: In the era of targeted therapies, the influence of aging on cancer management varies from one patient to another. Assessing individual frailty using geriatric tools has its limitations, and is not appropriate for all patients especially the youngest one. Thus, assessing the complementary value of a potential biomarker of individual aging is a promising field of investigation. The chronic myeloid leukemia model allows us to address this question with obvious advantages: longest experience in the use of tyrosine kinase inhibitors, standardization of therapeutic management and response with minimal residual disease and no effect on age-related diseases. Therefore, the aim of the BIO-TIMER study is to assess the biological age of chronic myeloid leukemia or non-malignant cells in patients treated with tyrosine kinase inhibitors and to determine its relevance, in association or not with individual frailty to optimize the personalised management of each patient.
METHODS: The BIO-TIMER study is a multi-center, prospective, longitudinal study aiming to evaluate the value of combining biological age determination by DNA methylation profile with individual frailty assessment to personalize the management of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Blood samples will be collected at diagnosis, 3 months and 12 months after treatment initiation. Individual frailty and quality of life will be assess at diagnosis, 6 months after treatment initiation, and then annually for 3 years. Tolerance to tyrosine kinase inhibitors will also be assessed during the 3-year follow-up. The study plans to recruit 321 patients and recruitment started in November 2023.
CONCLUSIONS: The assessment of individual frailty should make it possible to personalize the treatment and care of patients. The BIO-TIMER study will provide new data on the role of aging in the management of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors, which could influence clinical decision-making.
BACKGROUND: ClinicalTrials.gov , ID NCT06130787; registered on November 14, 2023.

UNASSIGNED: Hair products may be a source of harmful chemicals and have been linked to age-related health outcomes. We investigated whether the use of hair products is related to epigenetic age in a sample of Black (both Hispanic and non-Hispanic) and non-Hispanic White women.
UNASSIGNED: In a subset of 4358 participants aged 35-74 years from the Sister Study, we estimated cross-sectional associations between self-reported use of four chemical hair products (permanent dye, semipermanent dye, straighteners/relaxers, and hair permanents/body waves) in the year before enrollment (2003-2009) and three DNA methylation-based measures of epigenetic age (DunedinPACE, GrimAge age acceleration [GrimAgeAccel], and PhenoAge age acceleration [PhenoAgeAccel]) using survey-weighted multivariable linear regressions. Associations were estimated both overall and by self-identified race and ethnicity, adjusting for chronological age, socioeconomic and lifestyle factors, body mass index, menopausal status, and DNA methylation platform.
UNASSIGNED: Associations between the use of hair products and the three epigenetic age measures were largely null. Use of hair permanents/body waves was modestly associated with higher DunedinPACE among all participants (βever-never = 0.010; 95% confidence interval [CI] = 0.001, 0.019) and with lower PhenoAgeAccel among Black women (βever-never = -1.53; 95% CI = -2.84, -0.21).
UNASSIGNED: In this US-based study, we found little evidence of associations between chemical hair product use and epigenetic age in Black and non-Hispanic White women. Observed associations were modest and largely not supported by dose-response relationships or were inconsistent across epigenetic age measures. Previously observed associations between chemical hair product use and aging-related health outcomes may not be explained by the biological aging pathways captured by DunedinPACE, GrimAgeAccel, or PhenoAgeAccel. Alternative biological pathways are worth investigating in racially diverse samples.

Frailty reflects the heterogeneity in aging and may lead to the development of hypertension and heart disease, but the frailty-cardiovascular relationship and whether physical activity modifies this relationship in males and females are unclear. We tested whether higher frailty was positively associated with hypertension and heart disease in males and females and whether habitual movement mediated this relationship. The relationship between baseline frailty with follow-up hypertension and heart disease was investigated using the Canadian Longitudinal Study on Aging at 3-year follow-up data (males: n = 13,095; females: n = 13,601). Frailty at baseline was determined via a 73-item deficit-based index, activity at follow-up was determined via the Physical Activity Scale for the Elderly, and cardiovascular function was self-reported. Higher baseline frailty level was associated with a greater likelihood of hypertension and heart disease at follow-up, with covariate-adjusted odds ratios of 1.08-1.09 (all, P < 0.001) for a 0.01 increase in frailty index score. Among males and females, sitting time and strenuous physical activity were independently associated with hypertension, with these activity behaviors being partial mediators (except male-sitting time) for the frailty-hypertension relationship (explained 5-10% of relationship). The strength of this relationship was stronger among females. Only light-moderate activity partially mediated the relationship (∼6%) between frailty and heart disease in females, but no activity measure was a mediator for males. Higher frailty levels were associated with a greater incidence of hypertension and heart disease, and strategies that target increases in physical activity and reducing sitting may partially uncouple this relationship with hypertension, particularly among females.NEW & NOTEWORTHY Longitudinally, our study demonstrates that higher baseline frailty levels are associated with an increased risk of hypertension and heart disease in a large sample of Canadian males and females. Movement partially mediated this relationship, particularly among females.

Biological age is a construct that seeks to evaluate the biological wear and tear process of the organism that cannot be observed by chronological age. We estimate individuals\' biological age based on biomarkers from multiple systems and validate it through its association with mortality from natural causes. Biological age was estimated in 12,109 participants (6621 women and 5488 men) from the first visit of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) who had valid data for the biomarkers used in the analyses. Biological age was estimated using the Klemera and Doubal method. The difference between chronological age and biological age (Δage) was computed. Cox proportional hazard models stratified by sex were used to assess whether Δage was associated with mortality risk after a median follow-up of 9.1 years. The accuracy of the models was estimated by the area under the curve (AUC). Δage had equal mean for men and women, with greater variability for men. Cox models showed that every 1-year increase in Δage was associated with increased mortality in men (HR (95% CI) 1.21; 1.17-1.25) and women (HR (95% CI) 1.24; 1.15-1.34), independently of chronological age. Results of the AUC demonstrated that the predictive power of models that only included chronological age (AUC chronological age = 0.7396) or Δage (AUC Δage = 0.6842) was lower than those that included both, chronological age and Δage (AUC chronological age + Δage = 0.802), in men. This difference was not observed in women. We demonstrate that biological age is strongly related to mortality in both genders and is a valid predictor of death in Brazilian adults, especially among men.

OBJECTIVE: The relationship between alcohol consumption and age-related diseases is inconsistent. Biological age (BA) serves as both a precursor and a predictor of age-related diseases; however, longitudinal associations between alcohol consumption and BA in middle-aged and older people remain unclear. We measured whether there was a longitudinal association between drinking frequency and pure alcohol intake with BA among middle-aged and older people.
UNASSIGNED: This study involved two prospective cohort studies, set in Southwestern China and the United Kingdom. A total of 8046 participants from the China Multi-Ethnic Cohort study (CMEC) and 5412 participants from the UK Biobank (UKB), aged 30-79 years, took part, with complete data from two waves of clinical biomarkers.
METHODS: BA was calculated by the Klemera Doubal\'s method. Accelerated BA equalled BA minus chronological age. Drinking frequency and pure alcohol intake were obtained through self-reported questionnaires. Drinking frequency in the past year was classified as current non-drinking, occasional (monthly drinking) and regular (weekly drinking).
RESULTS: Compared with consistent current non-drinkers, more frequent drinkers [CMEC: β = 0.46, 95% confidence interval (CI) = 0.13-0.80; UKB: β = 0.65, 95% CI = 0.01-1.29)], less frequent drinkers (CMEC: β = 0.62, 95% CI = 0.37-0.87; UKB: β = 0.54, 95% CI = -0.01-1.09), consistent occasional drinkers (CMEC: β = 0.51, 95% CI = 0.23-0.79; UKB: β = 0.63, 95% CI = 0.13-1.13) and consistent regular drinkers (CMEC: β = 0.56, 95% CI = 0.17-0.95; UKB: β = 0.46, 95% CI = 0.00-0.91) exhibited increased accelerated BA. A non-linear relationship between pure alcohol intake and accelerated BA was observed among consistent regular drinkers.
CONCLUSIONS: In middle-aged and older people, any change in drinking frequency and any amount of pure alcohol intake seem to be positively associated with acceleration of biological ageing, compared with maintaining abstinence.