Dataset Information

DNA Methylation - and Telomere - Based Biological Age Estimation as Markers of Biological Aging in Donors Kidneys.

ABSTRACT: The biological age of an organ may represent a valuable tool for assessing its quality, especially in the elder. We examined the biological age of the kidneys [right (RK) and left kidney (LK)] and blood leukocytes in the same subject and compared these to assess whether blood mirrors kidney biological aging. Biological age was studied in n = 36 donors (median age: 72 years, range: 19-92; male: 42%) by exploring mitotic and non-mitotic pathways, using telomere length (TL) and age-methylation changes (DNAmAge) and its acceleration (AgeAcc). RK and LK DNAmAge are older than blood DNAmAge (RK vs. Blood, p = 0.0271 and LK vs. Blood, p = 0.0245) and RK and LK AgeAcc present higher score (this mean the AgeAcc is faster) than that of blood leukocytes (p = 0.0271 and p = 0.0245) in the same donor. TL of RK and LK are instead longer than that of blood (p = 0.0011 and p = 0.0098) and the increase in Remuzzi-Karpinski score is strongly correlated with kidney TL attrition (p = 0.0046). Finally, blood and kidney TL (p < 0.01) and DNAmAge (p < 0.001) were correlated. These markers can be evaluated in further studies as indicators of biological age of donor organ quality and increase the usage of organs from donors of advanced age therefore offering a potential translational research inkidney transplantation.

SUBMITTER: Pavanello S

PROVIDER: S-EPMC8984253 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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DNA Methylation - and Telomere - Based Biological Age Estimation as Markers of Biological Aging in Donors Kidneys.

Pavanello Sofia S Campisi Manuela M Rigotti Paolo P Bello Marianna Di MD Nuzzolese Erica E Neri Flavia F Furian Lucrezia L

Frontiers in medicine 20220323

The biological age of an organ may represent a valuable tool for assessing its quality, especially in the elder. We examined the biological age of the kidneys [right (RK) and left kidney (LK)] and blood leukocytes in the same subject and compared these to assess whether blood mirrors kidney biological aging. Biological age was studied in <i>n</i> = 36 donors (median age: 72 years, range: 19-92; male: 42%) by exploring mitotic and non-mitotic pathways, using telomere length (TL) and age-methylati ...[more]

PMID: 35402460

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Project description:Study questionAre reproductive characteristics associated with genome-wide DNA methylation and epigenetic age?Summary answerOur data suggest that increasing parity is associated with differences in blood DNA methylation and small increases in epigenetic age.What is known alreadyA study of 397 young Filipino women (ages 20-22) observed increasing epigenetic age with an increasing number of pregnancies.Study design, size, durationWe used data from 2356 non-Hispanic white women (ages 35-74) enrolled in the Sister Study cohort.Participants/materials, setting, methodsData on reproductive history were ascertained via questionnaire. Of the 2356 women, 1897 (81%) reported at least one live birth. Among parous women, 487 (26%) women reported ever experiencing a pregnancy complication. Three epigenetic clocks (i.e. Hannum, Horvath and Levine) and genome-wide methylation were measured in DNA from whole blood using Illumina's HumanMethylation450 BeadChip. We estimated association β-values and 95% CIs using linear regression.Main results and the role of chanceAll three epigenetic clocks showed weak associations between number of births and epigenetic age (per live birth; Hannum: β = 0.16, 95% CI = 0.02, 0.29, P = 0.03; Horvath: β = 0.12, 95% CI = -0.04, 0.27, P = 0.14; Levine: β = 0.27, 95% CI = 0.08, 0.45, P = 0.01); however, additional adjustment for current BMI attenuated the associations. Among parous women, a history of abnormal glucose tolerance during pregnancy was associated with increased epigenetic age by the Hannum clock (β = 0.96; 95% CI = 0.10, 1.81; P = 0.03) and Levine clocks (β = 1.69; 95% CI = 0.54, 2.84; P < 0.01). In epigenome-wide analysis, increasing parity was associated with methylation differences at 17 CpG sites (Bonferroni corrected P≤ 1.0 × 10-7).Limitations, reasons for cautionWe relied on retrospective recall to ascertain reproductive history and pregnancy complications.Wider implications of the findingsOur findings suggest that parity is associated with small increases in epigenetic age and with DNA methylation at multiple sites in the genome.Study funding/competing interest(s)This research was supported by the Intramural Research program of the NIH, National Institute of Environmental Health Sciences (Z01-ES049033, Z01-ES049032 and Z01-ES044055). None of the authors have a conflict of interest.Trial registration numberNot applicable.

Project description:BackgroundBiological heart age estimation can provide insights into cardiac aging. However, existing studies do not consider differential aging across cardiac regions.PurposeTo estimate biological age of the left ventricle (LV), right ventricle (RV), myocardium, left atrium, and right atrium using magnetic resonance imaging radiomics phenotypes and to investigate determinants of aging by cardiac region.Study typeCross-sectional.PopulationA total of 18,117 healthy UK Biobank participants including 8338 men (mean age = 64.2 ± 7.5) and 9779 women (mean age = 63.0 ± 7.4).Field strength/sequenceA 1.5 T/balanced steady-state free precession.AssessmentAn automated algorithm was used to segment the five cardiac regions, from which radiomic features were extracted. Bayesian ridge regression was used to estimate biological age of each cardiac region with radiomics features as predictors and chronological age as the output. The "age gap" was the difference between biological and chronological age. Linear regression was used to calculate associations of age gap from each cardiac region with socioeconomic, lifestyle, body composition, blood pressure and arterial stiffness, blood biomarkers, mental well-being, multiorgan health, and sex hormone exposures (n = 49).Statistical testMultiple testing correction with false discovery method (threshold = 5%).ResultsThe largest model error was with RV and the smallest with LV age (mean absolute error in men: 5.26 vs. 4.96 years). There were 172 statistically significant age gap associations. Greater visceral adiposity was the strongest correlate of larger age gaps, for example, myocardial age gap in women (Beta = 0.85, P = 1.69 × 10-26 ). Poor mental health associated with large age gaps, for example, "disinterested" episodes and myocardial age gap in men (Beta = 0.25, P = 0.001), as did a history of dental problems (eg LV in men Beta = 0.19, P = 0.02). Higher bone mineral density was the strongest associate of smaller age gaps, for example, myocardial age gap in men (Beta = -1.52, P = 7.44 × 10-6 ).Data conclusionThis work demonstrates image-based heart age estimation as a novel method for understanding cardiac aging.Evidence level1.Technical efficacyStage 1.

Dataset Information

DNA Methylation - and Telomere - Based Biological Age Estimation as Markers of Biological Aging in Donors Kidneys.

Publications

DNA Methylation - and Telomere - Based Biological Age Estimation as Markers of Biological Aging in Donors Kidneys.

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