Measure Of Biological Age Research Articles

The Val66Met variant of brain-derived neurotrophic factor is linked to reduced telomere length in a military population: a pilot study

In military populations, gene-environment interactions can influence performance and health outcomes. Brain-derived neurotrophic factor (BDNF) is a central nervous system protein that is important for neuronal function and synaptic plasticity. A BDNF single nucleotide polymorphism, rs6265, leads to an amino acid substitution of valine (Val) with methionine (Met) at codon 66 (Val66Met), which may influence an individual’s response to occupational stress, and predispose military members to psychological disorders. Telomere length (TL), a novel measure of biological aging, can be used as a biomarker of stress. Accordingly, telomere shortening may be a surrogate indicator of physiological weathering due to chronic disease and stressful life events. To increase our understanding about the potential effect of the Val66Met mutation on the human stress response, we evaluated the relationships between Val66Met, TL, and mental health symptoms in a military population. In this pilot study (N = 164), we observed an association between Val66Met and reduced TL (p = 0.048). There was no relationship between Val66Met and mental health symptoms. These results support the investigation of gene-environment interactions, and their potential influence on TL due to occupational stress such as military service.

Does PhenoAge acceleration impact adverse outcomes following major surgery (rehospitalization or death)? A genome-wide association study and mendelian randomisation

Abstract Background Biological aging reflects the state of an individual's cellular and molecular function, and is distinct from chronological age; which reflects the passage of time[1]. Validated measures of biological aging, such as Phenotypic aging (PhenoAge) estimated from nine routine clinical biomarkers, have been associated with increased risk of age-related diseases and mortality in cohort studies[2]. However, the potential causal relationship between them remains unclear. In this study, we aim to identify genetic variants associated with PhenoAge Acceleration (PhenoAgeAccl) and adverse outcome after surgery (rehospitalisation or death within 365-days] and assess the causal relationship between these two phenotypes using Mendelian Randomization framework. Objectives -Perform a genome-wide association study(GWAS) on adverse outcomes following major surgery. -Assess the potential causal relationship between PhenoAgeAccl and adverse outcomes following major surgery using Mendelian randomization analysis. Methods We conducted a GWAS via plink using participants from the UKBiobank (Application 77596) to generate summary statistics for 6509 participants who had undergone major surgery within 365 days of their baseline assessment date(3). For quality control, SNPs were excluded if they didn't meet the following criteria: (1) imputation information score <0.3 (2) minor allele frequency <1%, (3) Hardy–Weinberg equilibrium test p-value significant at the Bonferroni-corrected level. Summary statistics for PhenoAgeAccl was obtained from a previous GWAS of European descents[4]. Gene enrichment analysis was performed using Multi-marker Analysis of GenoMic Annotation (MAGMA) in Functional Mapping and Annotation (FUMA). Then, genetic instruments for PhenoAgeAccl and adverse outcomes following surgery were identified to conduct a summary-based Mendelian Randomisation [Assumptions are listed in Figure 1]. Results GWAS for adverse outcomes following major surgery identified 3 lead SNPs (rs1360618, rs11848297, rs7978) [Figure 2]. Gene-set analysis showed enrichment in the immune system, cell migration, fear response, and iron metabolism. For PhenoAge Acceleration, gene-set analysis showed enrichment in immune system, and cell signalling pathways. 17 SNPs were selected which were used for the Two-Sample MR. We found no causal relationship, as the beta coefficient for Inverse variance weighted was -0.308 [standard error - 0.075, p=0.68]. For every 5-year increase in PhenoAge compared to chronological age, the risk of emergency re-hospitalisation or death increased by 21% (HR 1.16 – 1.3, p < 0.001). Conclusion Gene-set analysis for adverse outcomes following major surgery showed enrichment in immune system, iron metabolism, and fear response which have all recently been associated with mortality post-surgery in cohort studies(4,5). No causal relationship between PhenoAgeAccel and mortality post-surgery was established.Mendelian Randomisation assumptionsManhattan plot adverse-outcomes post-sur

Association of biological aging with prostate cancer: insights from the National Health and Nutrition Examination Survey.

The link between biological aging and prostate cancer (PCa) risk, particularly as indicated by elevated prostate-specific antigen (PSA) levels, remains uncertain. This study utilized data from the National Health and Nutrition Examination Survey (2001-2010) to explore this association. Biological age was assessed using Klemera-Doubal method age (KDMAge) and phenotypic age (PhenoAge). PCa was identified through self-reported diagnoses, and highly probable PCa was determined by PSA levels. We analyzed the prevalence of PCa and PSA-defined highly probable PCa across quartiles of biological age measures using weighted chi-square and linear trend tests. Associations were evaluated using weighted multiple logistic regression models. Among 7,209 and 6,682 males analyzed, the overall weighted prevalence of PCa was 2.86%, increasing to 9.60% in those aged 65 and above. A significant rise in PCa prevalence was observed with higher quartiles of KDMAge or PhenoAge (P for trend < 0.001), particularly in those under 65. In this younger group, higher PhenoAge acceleration quartiles were linked to increased PCa prevalence and higher risk of PCa (OR = 1.50, P = 0.015) as well as highly probable PCa in those without a diagnosis (OR = 1.28, P = 0.031). These findings suggest that accelerated biological aging is associated with an increased risk of PCa and may indicate early risk as signaled by PSA levels, even in those without a PCa diagnosis.

Systematic Review of Associations between Anxiety, Depression, and Functional/Biological aging among Cancer Survivors.

Evidence suggests a mind-body component to aging, through which psychological distress from anxiety and depression drives molecular changes that promote early decline (ie, accelerated aging). Cancer survivors experience particularly high rates of anxiety and depression. Some survivors also have accelerated aging, though the relationships between anxiety/depression and aging are not clear. A synthesis of evidence is needed to understand the state of the science and impending priorities. PubMed, Embase, CINAHL, Web of Science, and PsycNet databases were searched for studies that measured associations between depression, anxiety, and non-chronological aging in cancer survivors (2012 to 2022). Data were methodologically evaluated. Survivorship studies were included if they were peer-reviewed, published in English from 2012-2022, and measured associations between anxiety/depression and aging. 51 studies were included. Just over half were cross-sectional (53%). Foci included functional (n = 35, 69%) and biological (n = 16, 31%). Functional aging measures included frailty, sarcopenia, geriatric assessment, and cognition. Biological aging measures included telomere length, telomerase, age-related inflammatory blood-based biomarkers, renal insufficiency, anemia, and DNA methylation. 223 associations were tested. Associations between anxiety, depression and aging were generally positive, though with varying strengths. Most compelling were associations between functional aging-depression. There were concerns for selection and measurement biases. Findings suggest positive associations between anxiety, depression and aging among cancer survivors. Future work is needed to clarify temporality, develop a consensus on the operationalization of aging, and diversify cohorts.

Accelerated Phenotypic Aging Associated With Hepatitis C Infection: Results From the U.S. National Health and Nutrition Examination Surveys 2015-2018.

Chronic hepatitis C virus (HCV) infection is associated with early onset of chronic diseases and increased risk of chronic disorders. Chronic viral infections have been linked to accelerated biological aging based on epigenetic clocks. In this study, we aimed to investigate the association between HCV infection and clinical measures of biological aging among 8 306 adults participating in the 2015-2018 waves of the National Health and Nutrition Examination Survey (NHANES). NHANES 2015-2018 participants aged 20 years and older who had complete data on clinical blood markers and HCV-related tests were included in the current study. We estimated biological age using 2 approaches including phenotypic age (PhenoAge) and allostatic load (AL) score based on 9 clinical biomarkers. After adjusting for demographic and other confounding factors, HCV antibody-positivity was associated with advanced PhenoAge (β = 2.43, 95% confidence interval: 1.51-3.35), compared with HCV antibody-negativity. Additionally, both active HCV infection (HCV RNA (+)) and resolved infection were associated with greater PhenoAge acceleration. The positive association with the AL score was not statistically significant. We did not observe any significant interactions of potential effect modifiers, including smoking and use of drug/needle injection, with HCV infection on measures of biological aging. Our findings suggest that HCV infection is independently associated with biological aging measured by phenotypic age in the U.S. general population. Further studies are warranted to confirm the findings.

Black Americans With Sickle Cell Disease (SCD) Demonstrate Accelerated Epigenetic Pace of Aging Compared to Black Americans Without SCD.

Sickle cell disease (SCD) is a chronic medical condition characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, and subsequently, end-organ damage and reduced survival. Because of this significant pathophysiology and early mortality, we hypothesized that patients with SCD are experiencing accelerated biological aging compared with individuals without SCD. We utilized the DunedinPACE measure to compare the epigenetic pace of aging in 131 Black Americans with SCD to 1391 Black American veterans without SCD. SCD patients displayed a significantly accelerated pace of aging (DunedinPACE mean difference of 0.057 points) compared with the veterans without SCD, whereby SCD patients were aging ≈0.7 months more per year than those without SCD (p = 4.49 × 10-8). This was true, even though the SCD patients were significantly younger according to chronological age than the individuals without SCD, making the epigenetic aging discrepancy even more apparent. This association became stronger when we removed individuals with posttraumatic stress disorder from the non-SCD group (p = 2.18 × 10-9), and stronger still when we restricted the SCD patients to those with hemoglobin SS and Sβ0 thalassemia genotypes (p = 1.61 × 10-10). These data support our hypothesis that individuals with SCD experience accelerated biological aging as measured by global epigenetic variation. The assessment of epigenetic measures of biological aging may prove useful to identify which SCD patients would most benefit from clinical interventions to reduce mortality.

The effects of age and frailty on the risks of end-stage renal disease, death, and severe infection in older adults with antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study

Frailty, a measure of biological age, might predict poor outcomes in older adults better than chronological age. We aimed to compare the effect of age and frailty on end-stage renal disease, death, and severe infection within 2 years of diagnosis in older adults with incident antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This retrospective cohort study included individuals aged 65 years or older from the Mass General Brigham ANCA-associated vasculitis cohort in the USA who were treated between Jan 1, 2002, and Dec 31, 2019. Individuals with a diagnosis of eosinophilic granulomatosis with polyangiitis were excluded from the analysis. Baseline frailty was measured with a claims-based frailty index using data collected in the year before the date of treatment initiation in individuals with at least one health-care encounter before baseline; individuals who did not have an encounter within the 12 months before baseline were classified as pre-frail. Incidence rates of end-stage renal disease or death and severe infections (ie, infections leading to hospital admission or death) at 2 years were estimated, and multivariable analyses were performed to compare the association of age and frailty with these outcomes. Cumulative incidence rates and an additive interaction analysis were used to assess the interaction of age and frailty groupings. Of the 234 individuals included, 136 (58%) were women, 98 (42%) were men, 198 (85%) were White, and 198 (85%) were positive for myeloperoxidase-specific ANCA. Frailty was present in 25 (22%) of 116 individuals aged 65-74 years and 44 (37%) of 118 aged 75 years or older. In the multivariable analysis, an age of 75 years or older was associated with an increased risk of end-stage renal disease or death (hazard ratio [HR] 4·50 [95% CI 1·83-11·09]), however, frailty was not (1·08 [0·50-2·36]). Both an age of 75 years or older (HR 2·52 [95% CI 1·26-5·04]) and frailty (8·46 [3·95-18·14]) were independent risk factors for severe infections. The effect of frailty on the incidence of end-stage renal disease or death was greater in individuals aged 65-74 years (frail vs non-frail or pre-frail incidence rate 7·5 cases vs 2·0 cases per 100 person-years) than in those aged 75 years or older (13·5 cases vs 16·0 cases per 100 person-years). The effect of frailty on the incidence of serious infections varied by age, with large differences observed among both individuals aged 65-74 years (frail vs non-frail or pre-frail incidence rate 38·9 cases vs 0·8 cases per 100 person-years) and individuals aged 75 years or older (61·9 cases vs 12·3 cases per 100 person-years). Despite the observed differences between the age groups, the additive interaction terms were not statistically significant for either frailty and end-stage renal disease or death (p for interaction=0·276) or frailty and serious infections (p for interaction=0·650). Adults with ANCA-associated vasculitis aged 75 years or older had a higher incidence of end-stage renal disease, death, and severe infections within 2 years of diagnosis than adults aged 65-74 years. Frailty, an approximation of biological age, was a risk factor for severe infection. Assessment beyond chronological age could better inform management decisions in older adults with ANCA-associated vasculitis. National Institutes of Health and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Salivary DNA methylation derived estimates of biological aging, cellular frequency and protein expression as predictors of oral mucositis severity and survival in head and neck cancer patients

BackgroundOral mucositis is a painful and debilitating condition that occurs in the majority of head and neck cancer patients receiving radiation and/or chemotherapy. While some patient and treatment related factors are known to contribute to the incidence and severity of disease, reliable biomarkers remain elusive. In the following study, we investigated the association of salivary DNA methylation derived biological aging, cellular frequency and protein concentration measures with the severity of oral mucositis and overall survival in a cohort of head and neck cancer (HNC) patients (n = 103). MethodsDNA methylation profiling was performed on saliva samples obtained prior to treatment. Biological aging measures included Horvath2, PhenoAge, FitAge and GrimAge, and cellular frequency included epithelial and specific immune cell populations. ResultsSevere mucositis (i.e. grade 3 or 4) occurred in nearly half of patients. For malignant HNC patients (n = 84), every 1-SD increase in GrimAge was associated with 2.62-times risk of severe mucositis (95 % CI: 1.38, 5.57), while a 1-SD increase in monocyte frequency was associated with a decreased risk (OR [95 %CI]: 0.40 [0.18, 0.80]). Over a median follow-up of 53 months, 39 of 103 participants died. Six protein scores (TNFSF14, GCSF, MATN3, GDF8, nCDase, TNF-β) were associated with survival at q < 0.15. ConclusionWe provide evidence that the risk-related biological aging measure GrimAge may be a useful predictor of mucositis severity in HNC patients. Salivary monocyte frequency may be protective against mucositis, and this measure could be used as a predictive biomarker while also providing clues into the pathobiology of the disease.

Exploring the Relationships between Lifestyle Patterns and Epigenetic Biological Age Measures in Men.

DNA methylation, validated as a surrogate for biological age, is a potential tool for predicting future morbidity and mortality outcomes. This study aims to explore how lifestyle patterns are associated with epigenetic changes in British men. Five biological age clocks were utilised to investigate the relationship between these epigenetic markers and lifestyle-related factors in a prospective study involving 221 participants. Spearman's correlation test, Pearson's correlation test, and univariate linear regression were employed for analysis. The results indicate that higher consumption of saturated fat and total daily calories, and a higher body mass index (BMI) are associated with accelerated biological aging. Conversely, higher vitamin D intake and a higher healthy lifestyle index (HLI) are linked to decelerated biological aging. These findings highlight the potential impact of specific lifestyle-related factors on biological aging and can serve as a reference for applying healthy lifestyle improvements in future disease prevention studies.

Animal Models Relevant for Geroscience: Current Trends and Future Perspectives in Biomarkers, and Measures of Biological Aging.

For centuries, aging was considered inevitable and immutable. Geroscience provides the conceptual framework to shift this focus toward a new view that regards aging as an active biological process, and the biological age of an individual as a modifiable entity. Significant steps forward have been made toward the identification of biomarkers for and measures of biological age, yet knowledge gaps in geroscience are still numerous. Animal models of aging are the focus of this perspective, which discusses how experimental design can be optimized to inform and refine the development of translationally relevant measures and biomarkers of biological age. We provide recommendations to the field, including: the design of longitudinal studies in which subjects are deeply phenotyped via repeated multilevel behavioral/social/molecular assays; the need to consider sociobehavioral variables relevant for the species studied; and finally, the importance of assessing age of onset, severity of pathologies, and age-at-death. We highlight approaches to integrate biomarkers and measures of functional impairment using machine learning approaches designed to estimate biological age as well as to predict future health declines and mortality. We expect that advances in animal models of aging will be crucial for the future of translational geroscience but also for the next chapter of medicine.

Biological Age, Chronological Age, and Survival in Pulmonary Fibrosis: A Causal Mediation Analysis.

Rationale: Accelerated biological aging has been implicated in the development of interstitial lung disease (ILD) and other diseases of aging but remains poorly understood. Objectives: To identify plasma proteins that mediate the relationship between chronological age and survival association in patients with ILD. Methods: Causal mediation analysis was performed to identify plasma proteins that mediated the chronological age-survival relationship in an idiopathic pulmonary fibrosis discovery cohort. Proteins mediating this relationship after adjustment for false discovery were advanced for testing in an independent ILD validation cohort and explored in a chronic obstructive pulmonary disease cohort. A proteomic-based measure of biological age was constructed and survival analysis performed, assessing the impact of biological age and peripheral blood telomere length on the chronological age-survival relationship. Measurements and Main Results: Twenty-two proteins mediated the chronological age-survival relationship after adjustment for false discovery in the idiopathic pulmonary fibrosis discovery cohort (n = 874), with 19 remaining significant mediators of this relationship in the ILD validation cohort (n = 983) and one mediating this relationship in the chronic obstructive pulmonary disease cohort. Latent transforming growth factor-β binding protein 2 and ectodysplasin A2 receptor showed the strongest mediation across cohorts. A proteomic measure of biological age completely attenuated the chronological age-survival association and better discriminated survival than chronological age. Results were robust to adjustment for peripheral blood telomere length, which did not mediate the chronological age-survival relationship. Conclusions: Molecular measures of aging completely mediate the relationship between chronological age and survival, suggesting that chronological age has no direct effect on ILD survival.

Epigenetic age acceleration and mortality risk prediction in U.S. adults.

Epigenetic clocks have emerged as novel measures of biological age and potential predictors of mortality. We aimed to test whether epigenetic age acceleration (EAA) estimated using different epigenetic clocks predict long-term overall, cardiovascular or cancer mortality. We analyzed data from 2,105 participants to the 1999-2002 National Health and Nutrition Examination Survey aged ≥50 years old who were followed for mortality through 2019. EAAs was calculated from the residuals of Horvath, Hannum, SkinBlood, Pheno, Zhang, Lin, Weidner, Vidal-Bralo and Grim epigenetic clocks regressed on chronological age. Using cox proportional hazards regression, we estimated the hazard ratio (HR) and 95% confidence interval (CI) for the association of EAA (per 5-year) and the DunedinPoAm pace of aging (per 10% increase) with overall, cardiovascular and cancer mortality, adjusting for covariates and white blood cell composition. During a median follow-up of 17.5 years, 998 deaths occurred, including 272 from cardiovascular disease and 209 from cancer. Overall mortality was most significantly predicted by Grim EAA (P < 0.0001; HR: 1.50, 95% CI: 1.32-1.71) followed by Hannum (P = 0.001; HR: 1.16, 95% CI: 1.07-1.27), Pheno (P = 0.001; HR: 1.13, 95% CI: 1.05-1.21), Horvath (P = 0.007; HR: 1.13, 95% CI: 1.04-1.22) and Vidal-Bralo (P = 0.008; HR: 1.13, 95% CI: 1.03-1.23) EAAs. Grim EAA predicted cardiovascular mortality (P < 0.0001; HR: 1.55, 95% CI: 1.29-1.86), whereas Hannum (P = 0.006; HR: 1.24, 95% CI: 1.07-1.44), Horvath (P = 0.02; HR: 1.18, 95% CI: 1.02-1.35) and Grim (P = 0.049; HR: 1.37, 95% CI: 1.00-1.87) EAAs predicted cancer mortality. DunedinPoAm pace of aging was associated with overall (P = 0.003; HR: 1.23, 95% CI: 1.08-1.38) and cardiovascular (P = 0.04; HR: 1.25, 95% CI: 1.01-1.55) mortality. In a U.S. representative sample, Horvath, Hannum, Pheno, Vidal-Bralo and Grim EAA all predicted overall mortality but only Grim EAA predicted cardiovascular mortality and Horvath, Hannum or Grim EAA predicted cancer mortality. Pace of aging predicted overall and cardiovascular mortality.

Higher serum uric acid as a risk factor for frailty in older adults: A nationwide population-based study.

Uric acid (UA), the terminal breakdown product of purine metabolism, possesses contradictory roles, functioning both as an inflammatory mediator and as an antioxidant. Its clinical relevance, particularly in geriatric populations, remains a topic of ongoing debate. Aiming to elucidate whether circulating UA is detrimental or beneficial to human health, we investigate the association between serum UA concentrations and the frailty index-a comprehensive measure of biological aging in a nationally representative cohort of community-dwelling older adults. We conducted a population-based, cross-sectional study utilizing data from the Korea National Health and Nutrition Examination Survey. The sample included 4268 participants aged 65years and above. A deficit accumulation frailty index (FI) was constructed using 38 items that assess physical, cognitive, psychological, and social domains. Based on the FI, participants were categorized into non-frail (FI≤0.15), pre-frail (0.15<FI≤0.25), or frail (FI>0.25). Serum UA levels were quantified through a colorimetric enzymatic assay. After controlling for confounders such as age, sex, socioeconomic status (including income and education level), lifestyle factors (smoking status), and medical history (hypertension, diabetes, dyslipidemia, stroke, cardiovascular diseases), and body mass index, serum UA levels were observed to be significantly higher in frail participants compared with their non-frail counterparts (P<0.001). Furthermore, serum UA concentrations demonstrated a positive correlation with the FI (P<0.001), and the odds ratio for frailty per 1mg/dL increase in serum UA was 1.22 (P<0.001). Additionally, older adults in the highest quartile of UA levels exhibited a significantly higher FI and 1.66-fold increased odds of frailty compared with those in the lowest quartile (P=0.011 and P=0.005, respectively). These findings suggest that elevated circulating UA levels may act as a pro-aging factor rather than an anti-aging one in older adults, highlighting its potential role in accelerating biological aging. The data further support the utility of serum UA as a potential blood-based biomarker for frailty in this demographic, contributing to the expanding evidence on its significance in geriatric health assessments.

The Relationship Between Central Obesity and Osteoarthritis in US Adults: The Mediating Role of Biological Aging Acceleration

Objective This study aims to investigate the association between central obesity and the risk of osteoarthritis, and the mediating role of biological age and biological aging advance in this relationship. Methods The study is based on data from the National Health and Nutrition Examination Survey (NHANES) for the years 2005–2018. Thirteen commonly used clinical traits were used to calculate the Klemera-Doubal method age (KDM-Age) and phenotypic age (Pheno-Age) as two measures of biological aging. Additionally, KDM-Age advance and Pheno-Age advance were calculated as two measures of biological aging advance. Weighted multivariable logistic regression was used to analyze the association between central obesity and the risk of osteoarthritis (OA). Mediation analysis was then applied to elucidate the role of biological aging and biological aging advance in this relationship. Results A total of 31,162 subjects aged ≥20 years were included in this study, of which 3,964 subjects reported having OA (14%). Compared to the Non-OA group, the OA group showed significantly higher proportions of central obesity, KDM-Age, KDM-Age advance, PhenoAge, and PhenoAge advance. Compared to the Non-central obesity group, the central obesity group had higher KDM-Age, KDM-Age advance, PhenoAge, PhenoAge advance, and a higher risk of OA (p < 0.05). Additionally, higher KDM-Age, KDM-Age advance, PhenoAge, and PhenoAge advance were positively correlated with the risk of OA (p < 0.05). Mediation analysis revealed that part of the association between central obesity and the risk of OA was mediated by KDM-Age, KDM-Age advance, PhenoAge, and PhenoAge advance (p < 0.05). Conclusion Central obesity increases the risk of OA, with part of this association being mediated by biological aging and biological aging advance.

Moderate BMI accumulation modified associations between blood benzene, toluene, ethylbenzene and xylene (BTEX) and phenotypic aging: mediating roles of inflammation and oxidative stress

The associations between blood benzene, toluene, ethylbenzene, and xylenes (BTEX) and biological aging among general adults remain elusive. The present study comprised 5780 participants from the National Health and Nutrition Examination Survey 1999–2010. A novel measure of biological aging, phenotypic age acceleration (PhenoAge.Accel), derived from biochemical markers was calculated. Weighted generalized linear regression and weighted quantile sum regression (WQS) were utilized to assess the associations between BTEX components and mixed exposure, and PhenoAge.Accel. The mediating roles of systemic immune-inflammation index (SII) and oxidative stress indicators (serum bilirubin and gamma-glutamyl transferase), along with the modifying effects of body mass index (BMI) were also examined. In the single-exposure model, the highest quantile of blood benzene (b = 0.89, 95%CI: 0.58 to 1.20), toluene (b = 0.87, 95%CI: 0.52 to 1.20), and ethylbenzene (b = 0.80, 95%CI: 0.46 to 1.10) was positively associated with PhenoAge.Accel compared to quantile 1. Mixed-exposure analyses revealed a consistent positive association between BTEX mixed exposure and PhenoAge.Accel (b = 0.88, 95%CI: 0.56 to 1.20), primarily driven by benzene (92.78%). The association between BTEX and PhenoAge.Accel was found to be partially mediated by inflammation and oxidative stress indicators (ranging from 3.2% to 13.7%). Additionally, BMI negatively modified the association between BTEX mixed exposure and PhenoAge.Accel, with a threshold identified at 36.2 kg/m^2. Furthermore, BMI negatively moderated the direct effect of BTEX mixed exposure on PhenoAge.Accel in moderated mediation models, while positively modified the link between SII and PhenoAge.Accel in the indirect path (binteraction = 0.04, 95%CI: 0.01 to 0.06). Overall, BTEX mixed exposure was associated with PhenoAge.Accel among US adults, with benzene may have reported most contribution, and inflammation and oxidative damage processes may partially explain this underlying mechanism. The study also highlighted the potential benefits of appropriate BMI increased. Additional large-scale cohort studies and experiments were necessary to substantiate these findings.

Association Between Phenotypic Age and the Risk of Mortality in Patients With Heart Failure: A Retrospective Cohort Study.

Chronological age (CA) is an imperfect proxy for the true biological aging state of the body. Asnovel measures of biological aging, Phenotypic age (PhenoAge) and Phenotypic age acceleration (PhenoAgeAccel), have been shown to identify morbidity and mortality risks in the general population. PhenoAge and PhenoAgeAccel might be associated with mortality in heart failure (HF) patients. This cohort study extracted adult data from the National Health and Nutrition Examination Survey (NHANES) databases. Weighted univariable and multivariable Cox models were performed to analyze the effect of PhenoAge and PhenoAgeAccel on all-cause mortality in HF patients, and hazard ratio (HR) with 95% confidence intervals (CI) was calculated. In total, 845 HF patients were identified, with 626 all-cause mortality patients. The findings suggested that (1) each 1- and 10-year increase in PhenoAge were associated with a 3% (HR = 1.03, 95% CI: 1.03-1.04) and 41% (HR = 1.41, 95% CI: 1.29-1.54) increased risk of all-cause mortality, respectively; (2) when the PhenoAgeAccel < 0 as reference, the ≥ 0 group was associated with higher risk of all-cause mortality (HR = 1.91, 95% CI = 1.49-2.45). Subgroup analyses showed that (1) older PhenoAge was associated with an increased risk of all-cause mortality in all subgroups; (2) when the PhenoAgeAccel < 0 as a reference, PhenoAgeAccel ≥ 0 was associated with a higher risk of all-cause mortality in all subgroups. Older PhenoAge was associated with an increased risk of all-cause mortality in HF patients. PhenoAge and PhenoAgeAccel can be used as convenient tools to facilitate the identification of at-risk individuals with HF and the evaluation of intervention efficacy.

Multinational evaluation of anthropometric age (AnthropoAge) as a measure of biological age in the USA, England, Mexico, Costa Rica, and China: a population-based longitudinal study.

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. 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). 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. 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.

Association between biological ageing and periodontitis: Evidence from a cross-sectional survey and multi-omics Mendelian randomization analysis.

To investigate the relationship and potential causality between biological ageing and periodontitis. We obtained the National Health and Nutrition Examination Survey (NHANES) and genome-wide association study (GWAS) summary statistics as well as single-cell sequencing data. Multivariate regression analysis based on cross-sectional data, Mendelian randomization (MR) and multi-omics integration analysis were employed to explore the causal association and potential molecular mechanisms between biological ageing and periodontitis. Additionally, two-step MR mediation analysis explored the risk factors in biological ageing-mediated periodontitis. We analysed data from 3189 participants in the NHANES data and found that higher biological age was associated with increased risk of periodontitis. MR analyses revealed causal associations between biological age measures and periodontitis risk. Frailty (odds ratio [OR] = 2.08, 95% confidence interval [CI]: 1.04-4.18, p = .039) and GrimAge acceleration (OR = 1.16, 95% CI: 1.01-1.32, p = .033) were causally associated with periodontitis risk, and these results were validated in a large-scale meta-periodontitis GWAS dataset. Additionally, the risk effects of body mass index, waist circumference and lifetime smoking on periodontitis were partially mediated by frailty and GrimAge acceleration. Evidence from cross-sectional survey and MR analysis suggests that biological ageing increases the risk of periodontitis. Additionally, improving the associated risk factors can help prevent both ageing and periodontitis.

Flooding exposure accelerated biological aging: a population-based study in the UK

Floods have been the most common type of disaster and are expected to increase in frequency and intensity due to climate change. Although there is growing evidence on the impacts of floods on human health, none has so far investigated the association between flooding exposure and biological aging acceleration. We collected data from 364 841 participants from the UK Biobank project. Flooding data before baseline were retrieved from the Dartmouth Flood Observatory and linked to each participant. Cumulative flooding exposure within six years before the baseline was calculated. We calculated the two biological aging measures at baseline: PhenoAge and Klemera-Doubal method biological age (KDM-BA) and assessed their associations with flooding exposure using mixed-effects linear regression models. We observed that participants exposed to higher levels of floods were more likely to have accelerated biological aging. The risks associated with flooding exposure could last for several years, with the highest cumulative effect observed over 0–4 years. In the fully adjusted model, per interquartile increase in cumulative flood exposure was associated with an increase of 0.24 years (95% CI: 0.14, 0.34) in PhenoAge acceleration and 0.14 years (95% CI: 0.07, 0.21) in KDM-BA acceleration over lag 0–4 years. The associations were consistent regardless of lifestyles, demographics, and socio-economic status. Our findings suggest that exposure to floods may lead to accelerated biological aging. Our work provides the basis for further understanding of the flood-related health impacts and suggests that public health policies and adaptation measures should be initiated in the short-, medium- and even long-term after flooding.

A proteomic signature of healthspan.

The focus of aging research has shifted from increasing lifespan to enhancing healthspan to reduce the time spent living with disability. Despite significant efforts to develop biomarkers of aging, few studies have focused on biomarkers of healthspan. We developed a proteomics-based signature of healthspan (healthspan proteomic score (HPS)) using data from the UK Biobank Pharma Proteomics Project (53,018 individuals and 2920 proteins). A lower HPS was associated with higher mortality risk and several age-related conditions, such as COPD, diabetes, heart failure, cancer, myocardial infarction, dementia, and stroke. HPS showed superior predictive accuracy for these outcomes compared to chronological age and biological age measures. Proteins associated with HPS were enriched in hallmark pathways such as immune response, inflammation, cellular signaling, and metabolic regulation. Our findings demonstrate the validity of HPS, making it a valuable tool for assessing healthspan and as a potential surrogate marker in geroscience-guided studies.