Biomarker Of Biological Aging Research Articles

Are pregnancy and parity associated with telomere length? A systematic review

BackgroundWomen's reproduction requires increased energy demands, which consequently may lead to cellular damage and aging. Hence, Telomere Length (TL), a biomarker of biological aging and health status may possibly serve as a biomarker of reproductive effort. The aim of this systematic review is to evaluate telomere dynamics throughout pregnancy and the association between parity and TL.MethodsA systematic search was conducted across seven databases including CINAHL, Cochrane, PsycINFO, Proquest, PubMed; Scopus; and Web of Science, using keywords and MeSH descriptors of parity and TL. Predefined inclusion and exclusion criteria were used to screen abstracts and titles. After the removal of duplicates, 3431 articles were included in the primary screening, narrowed to 194 articles included in the full-text screening. Consensus was reached for the 14 studies that were included in the final review, and the Newcastle–Ottawa scale (NOS) was utilized to assess the quality of the selected studies. A mini meta-analysis utilized JASP 0.17.3 software and included 4 applicable studies, comprising a total of 2564 participants to quantitatively assess the estimated effect size of parity on TL.ResultsOf the 11 studies reviewed on parity and TL, four demonstrated a negative correlation; one – a positive correlation and six -found no correlation. Studies demonstrating a negative correlation encompassed rigorous methodological practices possibly suggesting having more children is associated with enhanced telomere attrition. Of the four longitudinal studies assessing telomere dynamics throughout pregnancy, most found no change in TL from early pregnancy to postpartum suggesting pregnancy does not affect TL from early pregnancy to early postpartum. The meta-analysis revealed a negative, yet, non-significant effect, of the estimated effect size of parity on TL(ES = -0.009, p = 0.126, CI -0.021, 0.03).ConclusionsStudies assessing pregnancy, parity and TL yielded mixed results, most likely due to the different research methods utilized in each study. Improvements in study design to better understand the short-term effects of pregnancy on TL and the effect of parity on TL over time, include precise definitions of parity, comparisons of different age groups, inclusion of reproductive lifespan and statistically adjusting for potential confounders in the parity and TL relationship.

AI analysis of chest radiographs as a biomarker of biological age

AI analysis of chest radiographs as a biomarker of biological age

Retinal microvascular complexity as a putative biomarker of biological age: a pilot study.

Physiological changes associated with aging increase the risk for the development of age-related diseases. This increase is non-specific to the type of age-related disease, although each disease develops through a unique pathophysiologic mechanism. People who age at a faster rate develop age-related diseases earlier in their life. They have an older "biological age" compared to their "chronological age". Early detection of individuals with accelerated aging would allow timely intervention to postpone the onset of age-related diseases. This would increase their life expectancy and their length of good quality life. The goal of this study was to investigate whether retinal microvascular complexity could be used as a biomarker of biological age. Retinal images of 68 participants ages ranging from 19 to 82years were collected in an observational cross-sectional study. Twenty of the old participants had age-related diseases such as hypertension, type 2 diabetes, and/or Alzheimer's dementia. The rest of the participants were healthy. Retinal images were captured by a hand-held, non-mydriatic fundus camera and quantification of the microvascular complexity was performed by using Sholl's, box-counting fractal, and lacunarity analysis. In the healthy subjects, increasing chronological age was associated with lower retinal microvascular complexity measured by Sholl's analysis. Decreased box-counting fractal dimension was present in old patients, and this decrease was 2.1 times faster in participants who had age-related diseases (p = 0.047). Retinal microvascular complexity could be a promising new biomarker of biological age. The data from this study is the first of this kind collected in Montenegro. It is freely available for use.

Systemic inflammation and biological aging in the Health and Retirement Study

Chronic, low-level systemic inflammation associated with aging, or inflammaging, is a risk factor for several chronic diseases and mortality. Using data from the Health and Retirement Study, we generated a continuous latent variable for systemic inflammation from seven measured indicators of inflammation and examined associations with another biomarker of biological aging, DNA methylation age acceleration measured by epigenetic clocks, and 4-year mortality (N = 3,113). We found that greater systemic inflammation was positively associated with DNA methylation age acceleration for 10 of the 13 epigenetic clocks, after adjustment for sociodemographics and chronic disease risk factors. The latent variable for systemic inflammation was associated with 4-year mortality independent of DNA methylation age acceleration and was a better predictor of 4-year mortality than any of the epigenetic clocks examined, as well as mortality risk factors, including obesity and multimorbidity. Inflammaging and DNA methylation age acceleration may represent different biological processes contributing to mortality risk. Leveraging multiple measured inflammation markers to capture inflammaging is important for biology of aging research.

Exercise and epigenetic ages in older adults with myeloid malignancies

BackgroundOlder adults with myeloid malignancies are susceptible to treatment-related toxicities. Accelerated DNAm age, or the difference between DNA methylation (DNAm) age and chronological age, may be used as a biomarker of biological age to predict individuals at risk. In addition, cancer treatment can also lead to accelerated DNAm age. Exercise is a promising intervention to reduce or prevent functional, psychological, and cognitive impairments in older patients with myeloid malignancies, yet there is little evidence of the effects of exercise on DNAm age. We explored (1) the associations of accelerated DNAm age with physical, psychological, and cognitive functions at baseline; (2) changes in DNAm age from baseline to post-intervention; and (3) the associations of changes in accelerated DNAm age with changes in functions from baseline to post-intervention.MethodsWe enrolled older patients with myeloid malignancies to a single-arm pilot study testing a mobile health (mHealth) exercise intervention that combines an exercise program (EXCAP©®) with a mobile application over 2 cycles of chemotherapy (8–12 weeks). Patients completed measures of physical, psychological, and cognitive functions and provided blood samples for analyses of DNAm age at baseline and post-intervention. Paired t-tests or Wilcoxon signed rank tests assessed changes in DNAm ages, and Spearman’s correlation assessed the relationships between accelerated ages and functions.ResultsWe included 20 patients (mean age: 72 years, range 62–80). Accelerated GrimAge, accelerated PhenoAge, and DunedinPACE were stable from baseline to post-intervention. At baseline, DunedinPACE was correlated with worse grip strength (r = -0.41, p = 0.08). From baseline to post-intervention, decreases in accelerated GrimAge (r = -0.50, p = 0.02), accelerated PhenoAge (r = − 0.39, p = 0.09), and DunedinPace (r = − 0.43, p = 0.06) were correlated with increases in distance walked on 6-min walk test. Decreases in accelerated GrimAge (r = − 0.49, p = 0.03), accelerated PhenoAge (r = − 0.40, p = 0.08), and DunedinPace (r = − 0.41, p = 0.07) were correlated with increases in in grip strength.ConclusionsAmong older adults with myeloid malignancies receiving chemotherapy, GrimAge and PhenoAge on average are stable after a mHealth exercise intervention. Decreases in accelerated GrimAge, accelerated PhenoAge, and DunedinPACE over 8–12 weeks of exercise were correlated with increased physical performance. Future trials assessing the effects of exercise on treatment-related toxicities should evaluate DNAm age.Trial registration Clinicaltrials.gov identifier: NCT04981821.

Machine-learning derived measures of vascular and brain age are independently associated with cognitive function

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UiT The Arctic University of Norway, Northern Norway Regional Health Authority. Background/Introduction Machine learning models have been applied to magnetic resonance images of the brain to estimate brain age gap as a biomarker of biological aging. Because of its association with cognitive performance and neurological disorders, brain age gap has become an indicator of general brain health. Among others, cardiovascular risk factors are associated with brain health. Recently a novel non-invasive biomarker of vascular ageing has been proposed based on the application of a deep-learning algorithm to digitised 12-lead electrocardiograms. The difference between electrocardiogram predicted age and chronological age is defined as vascular age gap and has been shown to be associated with an adverse cardiovascular profile. However, the association of vascular age gap with cognitive health and dementias has not yet been examined. Purpose We apply a causal mediation framework to vascular age gap, brain age gap and cognitive function data obtained in the same individuals who took part in a population-based study in Norway. We hypothesise that cardiovascular risk factors encapsulated in vascular age gap can indirectly affect cognitive function by increasing the brain age gap. Methods We applied a deep learning algorithm (1) to electrocardiograms (N=7779, age 40-85 years) collected from the population-based sample in Norway (mean age 63.8 years, 45.3% men) to obtain a vascular age gap. For a subsample (N=1693) magnetic resonance images of the brain were also available and another deep neural network algorithm (2) was applied to obtain a biomarker of brain age. For 1678 participants with both vascular age gap and brain age gap available we used mediation analysis to test whether brain age gap mediates the effects of vascular age gap on cognitive function (as measured by mini mental status test, word memory test, digit–symbol coding test, tapping test) by estimating total, direct and indirect effects. Results We found a weak correlation (Pearson’s r = 0.12) between vascular age gap and brain age gap. Both age gaps were associated with cognitive scores capturing psychomotor speed, attention and mental flexibility. For a 1 standard deviation (7.3 years) increase in vascular age gap digit-symbol coding test score decreased by 0.63 (95%CI: -0.89, -0.36; p<0.001) points, and tapping test decreased by 0.36 (95%CI: -0.56, -0.14; p=0.001). Only 13% of effect of vascular age gap on cognitive test results was mediated by brain age gap. Conclusion(s) Vascular age gap was weakly associated with poorer cognitive functioning, and only 13% of this association was mediated by brain age gap. This suggests that cognitive decline linked to accumulated damage of the vascular system is not fully captured by structural changes in the brain. Further investigations of novel measures of biological aging in relation to cognitive decline are warranted as these may hold promise for improved understanding of mechanisms and clinical prediction.

Longer leukocyte telomere length increases cardiovascular mortality in type 2 diabetes patients.

Leukocyte telomere length (LTL), as a biomarker of biological aging, is associated with the prevalence and complications of diabetes. This study aims to investigate the associations between LTL and all-cause and cause-specific mortality in patients with type 2 diabetes. All participants with baseline LTL records were included from the National Health and Nutrition Examination Survey 1999-2002. Death status and its causes were ascertained for National Death Index based on International Classification of Diseases, Tenth Revision code. Cox proportional hazards regression models were established to estimate the hazard ratios (HRs) of LTL associating with all-cause and cause-specific mortality. The study enrolled 804 diabetic patients with the mean follow-up of 14.9 ± 2.59 years. There were 367 (45.6%) all-cause deaths, 80 (10.0%) cardiovascular deaths, and 42 (5.2%) cancer-related deaths. Longer LTL was associated with reduced all-cause mortality, whereas this association disappeared after adjusting for other variables. Compared with the lowest tertiles of LTL, the multivariable-adjusted hazard ratio of cardiovascular mortality was 2.11 (95% confidence interval [CI] 1.31-3.39; p < .05) in the highest tertiles. In terms of cancer mortality, the highest tertile was negatively correlated with the risk of cancer mortality (HR 0.58 [95% CI 0.37, 0.91], p < .05). In conclusion, LTL was independently associated with the risk of cardiovascular mortality in patients with type 2 diabetes and was negatively correlated with the risk of cancer mortality. Telomere length may be a predictor of cardiovascular mortality in diabetes.

Association of telomere length and mitochondrial DNA copy number, two biomarkers of biological aging, with the risk of venous thromboembolism

BackgroundVenous thromboembolism (VTE) is the third most common cardiovascular disease and occurs in all age groups, albeit the risk increases considerably with age. Previous research indicates mitochondrial dysfunction and telomere shortening in cardiovascular aging. However, in the context of VTE this has not been investigated in detail. AimWe aimed to explore biomarkers reflecting biological aging (i.e. human mitochondrial DNA copy number (mtDNA) and telomere length) and their association with VTE. MethodsmtDNA and telomere length were measured in a case-control study of 116 patients with a history of VTE and 128 age- and sex-matched healthy individuals from isolated blood using a qPCR-based assay kit. Cases had at least one unprovoked VTE event and were enrolled no earlier than 3 months after the last VTE event. ResultsThe mtDNA copy number was significantly lower in VTE cases compared to controls (median [IQR]: 663 per diploid cells [78.75–2204.5] vs. 2832 per diploid cells [724–4350]; p < 0.001). After adjustment for age, sex, BMI, and smoking, mtDNA copy number was independently associated with VTE risk (odds ratio per increase in 400 mtDNA per diploid cell: 0.889, 95%CI 0.834–0.947). mtDNA copy numbers were significantly different between women and men (2375 [455–3737] women vs. 893 [152–3154] men; p < 0.001). The analysis of telomere length showed no significant difference between patients and healthy controls. ConclusionLower mtDNA levels were found in patients with VTE compared to controls, indicating an association of biological aging with risk of VTE.

Abstract A009: Association of neighborhood disadvantage with biomarkers of biological aging and chronic stress among breast cancer survivors. [R

Abstract Living in a disadvantaged neighborhood is associated with adverse outcomes among breast cancer patients, but the underlying pathway is still unclear. Limited evidence has suggested that chronic stress and accelerated biological aging may play an important role. Biological aging and chronic stress are closely related, and both associated with mitochondrial dysfunction, abnormal DNA methylation, telomere shortening, etc. For example, allostatic load (AL), a biomarker of chronic stress, increases with age as a result of the cumulative effects of allostasis across the lifespan. In this study, we attempted to take the first step by evaluating the association of neighborhood disadvantage with biomarkers of chronic stress and biological aging among breast cancer patients. Using a sub-sample of 906 women with newly diagnosed breast cancer at M.D. Anderson, we examined whether levels of AL and selected biological aging biomarkers (global DNA methylation, telomere length, etc.) were affected by neighborhood disadvantage. The Area Deprivation Index (ADI) was used to measure the levels of neighborhood disadvantage. Telomere length and global DNA methylation in leukocytes were measured by qPCR and ELISA, respectively. We used 17 factors that represent the activity of five physiological systems to construct the AL score. Based on the median ADI at the national level, the study population was divided into low and high ADI groups. Overall, breast cancer patients from the high ADI group were more likely to be younger and non-Hispanic Black than those from the low ADI group (P&amp;lt;0.001). They were also more likely to have higher stage and poorly differentiated breast tumors (P=0.029 and 0.019, respectively). For the relationship with markers, compared to the low ADI group, high ADI group had higher median levels of AL (P=0.046) and lower median levels of global DNA methylation (P&amp;lt;0.001). Higher AL was considered as an indicator of increased chronic stress. Compared to their counterparts, those from the high ADI group were 20% and 32% more likely to have increased AL and telomerase activity, respectively, and 51% less likely to have increased levels of global DNA methylation. We also found that ADI was inversely correlated with telomere length. Additionally, we found that the significant associations of AL and global DNA methylation with ADI group were observed in non-Hispanic Whites and Blacks, but not in Hispanics. Lastly, using the mediation analysis, we found that decreased global DNA methylation mediated 6.52 and 7.98% of the association between higher ADI group with stage III and poorly differentiated tumor (P=0.037 and 0.023), respectively. In summary, we observed that neighborhood disadvantage was associated with more aggressive breast tumor characteristics, and influenced the levels of AL and global DNA methylation among breast cancer patients. Our findings suggest that neighborhood disadvantage is biologically embedded in molecular level and associated with accelerated biological aging and increased chronic stress among breast cancer patients. Citation Format: Jie Shen, Hua Zhao, Bernard Fuemmeler, Vanessa Sheppard, Harry Bear. Association of neighborhood disadvantage with biomarkers of biological aging and chronic stress among breast cancer survivors. [R] [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A009.

Heritability of the glycan clock of biological age.

Immunoglobulin G is posttranslationally modified by the addition of complex N-glycans affecting its function and mediating inflammation at multiple levels. IgG glycome composition changes with age and health in a predictive pattern, presumably due to inflammaging. As a result, a novel biological aging biomarker, glycan clock of age, was developed. Glycan clock of age is the first of biological aging clocks for which multiple studies showed a possibility of clock reversal even with simple lifestyle interventions. However, none of the previous studies determined to which extent the glycan clock can be turned, and how much is fixed by genetic predisposition. To determine the contribution of genetic and environmental factors to phenotypic variation of the glycan clock, we performed heritability analysis on two TwinsUK female cohorts. IgG glycans from monozygotic and dizygotic twin pairs were analyzed by UHPLC and glycan age was calculated using the glycan clock. In order to determine additive genetic, shared, and unique environmental contributions, a classical twin design was applied. Heritability of the glycan clock was calculated for participants of one cross-sectional and one longitudinal cohort with three time points to assess the reliability of measurements. Heritability estimate for the glycan clock was 39% on average, suggesting a moderate contribution of additive genetic factors (A) to glycan clock variation. Remarkably, heritability estimates remained approximately the same in all time points of the longitudinal study, even though IgG glycome composition changed substantially. Most environmental contributions came from shared environmental factors (C), with unique environmental factors (E) having a minor role. Interestingly, heritability estimates nearly doubled, to an average of 71%, when we included age as a covariant. This intervention also inflated the estimates of unique environmental factors contributing to glycan clock variation. A complex interplay between genetic and environmental factors defines alternative IgG glycosylation during aging and, consequently, dictates the glycan clock's ticking. Apparently, environmental factors (including lifestyle choices) have a strong impact on the biological age measured with the glycan clock, which additionally clarifies why this aging clock is one of the most potent biomarkers of biological aging.

A Blood-Based Molecular Clock for Biological Age Estimation.

In the last decade, extensive efforts have been made to identify biomarkers of biological age. DNA methylation levels of ELOVL fatty acid elongase 2 (ELOVL2) and the signal joint T-cell receptor rearrangement excision circles (sjTRECs) represent the most promising candidates. Although these two non-redundant biomarkers echo important biological aspects of the ageing process in humans, a well-validated molecular clock exploiting these powerful candidates has not yet been formulated. The present study aimed to develop a more accurate molecular clock in a sample of 194 Italian individuals by re-analyzing the previously obtained EVOLV2 methylation data together with the amount of sjTRECs in the same blood samples. The proposed model showed a high prediction accuracy both in younger individuals with an error of about 2.5 years and in older subjects where a relatively low error was observed if compared with those reported in previously published studies. In conclusion, an easy, cost-effective and reliable model to measure the individual rate and the quality of aging in human population has been proposed. Further studies are required to validate the model and to extend its use in an applicative context.

Early emergence of sexual dimorphism in offspring leukocyte telomere length was associated with maternal and children’s glucose metabolism—a longitudinal study

BackgroundLeukocyte telomere length (LTL) is suggested to be a biomarker of biological age and reported to be associated with metabolic diseases such as type 2 diabetes. Glucose metabolic traits including glucose and insulin levels have been reported to be associated with LTL in adulthood. However, there is relatively little research focusing on children’s LTL and the association with prenatal exposures. This study investigates the relationship between maternal and offspring glucose metabolism with offspring LTL in early life.MethodsThis study included 882 mother-child pairs from the HAPO Hong Kong Field Centre, with children evaluated at age 7.0 ± 0.4 (mean ± SD) years. Glucose metabolic traits including maternal post-load glucose during pregnancy, children’s glucose and insulin levels, and their derived indices at follow-up were measured or calculated. Offspring LTL was assessed using real-time polymerase chain reaction.ResultsSex- and age-adjusted children’s LTL was found to be associated with children’s HOMA-IR (β=−0.046 ± 0.016, p=0.005). Interestingly, both children’s and maternal post-load glucose levels were positively associated with children’s LTL. However, negative associations were observed between children’s LTL and children’s OGTT insulin levels. In addition, the LTL in females was more strongly associated with pancreatic beta-cell function whilst LTL in males was more strongly associated with OGTT glucose levels.ConclusionsOur findings suggest a close association between maternal and offspring glucose metabolic traits with early life LTL, with the offspring sex as an important modifier of the disparate relationships in insulin production and response.

Rationale and design of the Anal HPV, HIV and Aging (AHHA) study: Protocol for a prospective study of anal HPV infection and HSIL among men who have sex (MSM) or trans women living with and without HIV, ages 50 and older.

More than half of people living with HIV in the US are 50+ years old. Despite the benefits of antiretroviral therapy, older individuals with HIV are at higher risk for illnesses than their HIV-negative counterparts. Anal cancer, anal high-grade squamous intraepithelial lesions (HSIL), and anal HPV-16 infection occur most frequently among men who have sex with men living with HIV (MSMLWH). Men aged 60+ are 3-fold more likely to be diagnosed with anal cancer compared with younger men. Despite the increasing risk of anal cancer with age and HIV, little is known about the relationships among aging, HPV infection, HSIL and HIV. The Anal HPV, HIV, and Aging (AHHA) Study is a two-stage project to evaluate the relationships among anal HPV infection, HSIL, HIV infection, and biomarkers of biological aging in MSM or trans women over the age of 50 years. Stage 1 will estimate the cross-sectional prevalence of both anal HPV infection and HSIL, based on outcomes of anal HPV DNA testing, and high-resolution anoscopy with biopsy. We will also study associations with study outcomes and serological biomarkers of inflammation (interleukin-6, C-reactive protein, D-dimer) and with the Veterans Aging Cohort Study Index and the Fried Frailty Phenotype using multivariable models. Participants living with HIV (n = 150) and HIV-negative participants (n = 150) will be enrolled. The 3-year Stage 2 longitudinal sample restricted to HSIL-negative and anal HPV-16 DNA-negative participants will estimate the 3-year incidence of both anal HSIL and anal HPV, stratified by HIV status through Cox proportional hazards regression. The effect of biomarkers of inflammation and markers of aging on study outcomes will be evaluated through multivariable repeated measures models stratified by HIV status. This protocol was approved by the University of California, San Francisco Institutional Review Board (IRB: 16-18966). Results will be disseminated through presentations at national/international scientific conferences and publication in peer-reviewed journals.

Short-Term Exposure of PM2.5 and Epigenetic Aging: A Quasi-Experimental Study.

Epigenetic age (EA) is an emerging DNA methylation-based biomarker of biological aging, but whether EA is causally associated with short-term PM2.5 exposure remains unknown. We conducted a quasi-experimental study of 26 healthy adults to test whether short-term PM2.5 exposure accelerates seven EAs with three health examinations performed before, during, and after multiple PM2.5 pollution waves. Seven EAs were derived from the DNA methylation profiles of the Illumina HumanMethylationEPIC BeadChip from CD4+ T-helper cells. We found that an increase of 10 μg/m3 in the 0-24 h personal PM2.5 exposure prior to health examinations was associated with a 0.035, 0.035, 0.050, 0.055, 0.052, and 0.037-unit increase in the changes of z-scored DNA methylation age acceleration (AA,Horvath), AA (Hannum), AA (GrimAge), DunedinPoAm, mortality risk score (MS), and epiTOC, respectively (p-values < 0.05). The same increase in the 24-48 h average personal PM2.5 exposure yielded smaller effects but was still robustly associated with the changes in AA (GrimAge), DunedinPoAm, and MS. Such acute aging effects of PM2.5 were mediated by the changes in several circulating biomarkers, including EC-SOD and sCD40L, with up to ∼28% mediated proportions. Our findings demonstrated that short-term PM2.5 exposure could accelerate aging reflected by DNA methylation profiles via blood coagulation, oxidative stress, and systematic inflammation.

Residential green space and waist circumference affect telomere shortening in childhood: the longitudinal ChiBS study

BackgroundTelomere shortening, recognised as one of the most well known biomarkers of biological ageing, is susceptible to various environmental and lifestyle factors, encompassed in the exposome. Research shows that telomere length is substantially determined early in life and that exposures in childhood can have important consequences in setting telomere length later in life and thus the lifespan of an individual. We explored the associations between 17 exposures and longitudinal telomere change in a child population. MethodsChildren up to the age of 9 years, from Aalter, Belgium, were enrolled in 2008 and 2010 and followed-up for 5 or 7 years (up to 2015). Relative telomere length was measured at baseline (2008 or 2010) and at follow-up, in 2015, through quantitative real-time PCR. Exposures and lifestyle factors comprised: body-mass index, waist circumference, dietary habits (ie, sugar-rich and fat-rich food intake and vegetables and fruit intake), psychosocial stress (ie, negative events, emotions, and behaviour), sleep duration, physical activity, and residential environmental quality (long-term black carbon and particulate matter exposure and residential green space). Green space was estimated from high-resolution land cover data within several buffers (50–3000 m) around the child's residence. Cross-sectional and longitudinal analyses were done by means of linear regression models, adjusting for length of follow-up, age, sex, and socioeconomic status. Effect size was expressed as β, the standardised regression coefficient of the linear regression, and was calculated by multiplying the unstandardised regression coefficient by the standard deviation of the predictor variable and dividing by the standard deviation of the outcome variable. Written informed consent was obtained from all parents. Children aged 12 years and older also provided written informed consent. Children younger than 12 years gave verbal consent. Findings150 children (77 [51%] boys and 73 [49%] girls) aged 2·8–10·3 years (median 5·9 years [IQR 4·9–7·1]) at baseline were included in the longitudinal analysis, which showed that higher residential green space at baseline was associated with inferior telomere shortening (β=0·261; p=0·0018), whereas a higher baseline waist circumference was associated with more telomere attrition (β=–0·287; p=0·0015). These predictors were confirmed via lasso variable selection and correction for multiple testing. In addition, children with more unhealthy exposures had significantly more telomere shortening over the follow-up period than did children with less unhealthy baseline exposures (β=–0·200; p=0·017). InterpretationResidential green space and waist circumference were identified as predictors of telomere shortening in childhood. These results further showcase the benefits of a healthy lifestyle from an early age and the importance of a green environment in promoting molecular longevity from childhood onwards. FundingResearch Foundation Flanders (Brussels, Belgium; project number G073315N).

Serum lead, mercury, manganese, and copper and DNA methylation age among adults in Detroit, Michigan.

Although the effects of lead, mercury, manganese, and copper on individual disease processes are well understood, estimating the health effects of long-term exposure to these metals at the low concentrations often observed in the general population is difficult. In addition, the health effects of joint exposure to multiple metals are difficult to estimate. Biological aging refers to the integrative progression of multiple physiologic and molecular changes that make individuals more at risk of disease. Biomarkers of biological aging may be useful to estimate the population-level effects of metal exposure prior to the development of disease in the population. We used data from 290 participants in the Detroit Neighborhood Health Study to estimate the effect of serum lead, mercury, manganese, and copper on three DNA methylation-based biomarkers of biological aging (Horvath Age, PhenoAge, and GrimAge). We used mixed models and Bayesian kernel machine regression and controlled for participant sex, race, ethnicity, cigarette use, income, educational attainment, and block group poverty. We observed consistently positive estimates of the effects between lead and GrimAge acceleration and mercury and PhenoAge acceleration. In contrast, we observed consistently negative associations between manganese and PhenoAge acceleration and mercury and Horvath Age acceleration. We also observed curvilinear relationships between copper and both PhenoAge and GrimAge acceleration. Increasing total exposure to the observed mixture of metals was associated with increased PhenoAge and GrimAge acceleration and decreased Horvath Age acceleration. These findings indicate that an increase in serum lead or mercury from the 25th to 75th percentile is associated with a ∼0.25-year increase in two epigenetic markers of all-cause mortality in a population of adults in Detroit, Michigan. While few of the findings were statistically significant, their consistency and novelty warrant interest.

Contribution of Biological Age–Predictive Biomarkers to Nutrition Research: A Systematic Review of the Current Evidence and Implications for Future Research and Clinical Practice

ABSTRACTThe global population is living longer; however, not everyone ages at the same rate with regard to their physical and cognitive abilities and their vulnerability to certain diseases and death. This review aimed to synthesize the contribution of biological age–predictive biomarkers to nutrition research and highlight the implications for future research and clinical practice. MEDLINE, CINAHL, and Cochrane CENTRAL were systematically searched on 30 September 2021 for randomized controlled trials and cross-sectional studies examining the association between nutrition and biological age in older adults reporting on genetic, clinical, or molecular biomarkers of biological aging. Cochrane's ROB 2 and ROBINS-I were used to assess the quality of included studies. Synthesis was undertaken narratively. Of 1245 records identified from the search, 13 studies from 8 countries and territories, involving 5043 participants, were included. Seven studies assessed associations between nutrient food intake and telomere attrition, reporting protective effects for branched-chain amino acids, calcium and vitamin D, and a diet of a lower inflammatory index; whereas they found shorter telomeres in people consuming more processed foods and arachidonic acid and other proinflammatory compounds. Five studies examined the associations between plasma nutrition biomarkers and cognitive function, and found a protective effect for HDL cholesterol, lycopene, carotenoids, ω-3 and ω-6 fatty acids, and vitamins B, C, D, and E; whereas trans fatty acids and fibrinogen correlated with a decline in cognitive function. One study used Horvath's clock and reported the epigenetic rejuvenation effect of a Mediterranean diet. In conclusion, biological aging was negatively associated with an anti-inflammatory diet. However, a few studies did not control for the confounding effect of other lifestyle factors. Future research should address this and also assess the synergistic effect of different nutrients, their combinations, and evaluate their dose–response relations. Nutrition practice can incorporate updated screening procedures for older people that include relevant biological aging nutrition markers, leading to anti-aging precision nutrition therapy. The methodology of this systematic review was registered in PROSPERO (CRD42021288122).

Lipidomics profiling of biological aging in American Indians: the Strong Heart Family Study.

Telomeres shorten with age and shorter leukocyte telomere length (LTL) has been associated with various age-related diseases. Thus, LTL has been considered a biomarker of biological aging. Dyslipidemia is an established risk factor for most age-related metabolic disorders. However, little is known about the relationship between LTL and dyslipidemia. Lipidomics is a new biochemical technique that can simultaneously identify and quantify hundreds to thousands of small molecular lipid species. In a large population comprising 1843 well-characterized American Indians in the Strong Heart Family Study, we examined the lipidomic profile of biological aging assessed by LTL. Briefly, LTL was quantified by qPCR. Fasting plasma lipids were quantified by untargeted liquid chromatography-mass spectrometry. Lipids associated with LTL were identified by elastic net modeling. Of 1542 molecular lipids identified (518 known, 1024 unknown), 174 lipids (36 knowns) were significantly associated with LTL, independent of chronological age, sex, BMI, hypertension, diabetes status, smoking status, bulk HDL-C, and LDL-C. These findings suggest that altered lipid metabolism is associated with biological aging and provide novel insights that may enhance our understanding of the relationship between dyslipidemia, biological aging, and age-related diseases in American Indians.

Association between COVID-19 and telomere length: A bidirectional Mendelian randomization study.

Several traditional observational studies suggested an association between COVID‐19 and leukocyte telomere length (LTL), a biomarker for biological age. However, whether there was a causal association between them remained unclear. We aimed to investigate whether genetically predicted COVID‐19 is related to the risk of LTL, and vice versa. We performed bidirectional Mendelian randomization (MR) study using summary statistics from the genome‐wide association studies of critically ill COVID‐19 (n = 1 388 342) and LTL (n = 472 174) of European ancestry. The random‐effects inverse‐variance weighted estimation method was applied as the primary method with several other estimators as complementary methods. Using six single‐nucleotide polymorphisms (SNPs) of genome‐wide significance as instrumental variables for critically ill COVID‐19, we did not find a significant association of COVID‐19 on LTL (β = 0.0075, 95% confidence interval [CI]: −0.018 to 0.021, p = 0.733). Likewise, using 97 SNPs of genome‐wide significance as instrumental variables for LTL, we did not find a significant association of LTL on COVID‐19 (odds ratio = 1.00, 95% CI: 0.79–1.28, p = 0.973). Comparable results were obtained using MR‐Egger regression, weighted median, and weighted mode approaches. We did not find evidence to support a causal association between COVID‐19 and LTL in either direction.

Measuring biological age using omics data.

Age is the key risk factor for diseases and disabilities of the elderly. Efforts to tackle age-related diseases and increase healthspan have suggested targeting the ageing process itself to 'rejuvenate' physiological functioning. However, achieving this aim requires measures of biological age and rates of ageing at the molecular level. Spurred by recent advances in high-throughput omics technologies, a new generation of tools to measure biological ageing now enables the quantitative characterization of ageing at molecular resolution. Epigenomic, transcriptomic, proteomic and metabolomic data can be harnessed with machine learning to build 'ageing clocks' with demonstrated capacity to identify new biomarkers of biological ageing.