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Morphometric skin characteristics dependent on chronological and biological age: the Leiden Longevity Study.

ABSTRACT: The effect of chronological age on skin characteristics is readily visible, and its underlying histological changes have been a field of study for several years. However, the effect of biological age (i.e. a person's rate of ageing compared to their chronological age) on the skin has so far only been studied in facial photographs. Skin biopsies obtained from middle-aged offspring of nonagenarian siblings that are genetically enriched for longevity were compared to their partners who represent the general Dutch population. Though of the same chronological age, the offspring were previously observed to be of a younger biological age than their partners. The biopsies were analysed on several aspects epidermal and elastic fibre morphology. We investigated whether these skin characteristics were dependent on chronological age, familial longevity (the difference between the offspring and partners) and Framingham heart risk scores, adjusted for external stressors. A decreased thickness and flattening of the epidermis as well as an increased amount of elastic fibres in the reticular dermis were observed with chronological age (P < 0.001, P < 0.001 and P = 0.03, respectively), but no effect of familial longevity was found. The Framingham heart risk score was associated with some skin characteristics. A slower rate of skin ageing does not mark offspring from nonagenarian siblings. Epidermal and elastic fibre morphometric characteristics are not a potential marker for familial longevity in middle-aged subjects enriched for familial longevity.

SUBMITTER: Waaijer ME

PROVIDER: S-EPMC3528376 | biostudies-other | 2012 Dec

REPOSITORIES: biostudies-other

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Morphometric skin characteristics dependent on chronological and biological age: the Leiden Longevity Study.

Waaijer Mariette E C ME Gunn David A DA Catt Sharon D SD van Ginkel Michael M de Craen Anton J M AJ Hudson Nicole M NM van Heemst Diana D Slagboom P Eline PE Westendorp Rudi G J RG Maier Andrea B AB

Age (Dordrecht, Netherlands) 20110910 6

The effect of chronological age on skin characteristics is readily visible, and its underlying histological changes have been a field of study for several years. However, the effect of biological age (i.e. a person's rate of ageing compared to their chronological age) on the skin has so far only been studied in facial photographs. Skin biopsies obtained from middle-aged offspring of nonagenarian siblings that are genetically enriched for longevity were compared to their partners who represent th ...[more]

PMID: 21909657

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Project description:BackgroundEpigenetic clocks can track both chronological age (cAge) and biological age (bAge). The latter is typically defined by physiological biomarkers and risk of adverse health outcomes, including all-cause mortality. As cohort sample sizes increase, estimates of cAge and bAge become more precise. Here, we aim to develop accurate epigenetic predictors of cAge and bAge, whilst improving our understanding of their epigenomic architecture.MethodsFirst, we perform large-scale (N = 18,413) epigenome-wide association studies (EWAS) of chronological age and all-cause mortality. Next, to create a cAge predictor, we use methylation data from 24,674 participants from the Generation Scotland study, the Lothian Birth Cohorts (LBC) of 1921 and 1936, and 8 other cohorts with publicly available data. In addition, we train a predictor of time to all-cause mortality as a proxy for bAge using the Generation Scotland cohort (1214 observed deaths). For this purpose, we use epigenetic surrogates (EpiScores) for 109 plasma proteins and the 8 component parts of GrimAge, one of the current best epigenetic predictors of survival. We test this bAge predictor in four external cohorts (LBC1921, LBC1936, the Framingham Heart Study and the Women's Health Initiative study).ResultsThrough the inclusion of linear and non-linear age-CpG associations from the EWAS, feature pre-selection in advance of elastic net regression, and a leave-one-cohort-out (LOCO) cross-validation framework, we obtain cAge prediction with a median absolute error equal to 2.3 years. Our bAge predictor was found to slightly outperform GrimAge in terms of the strength of its association to survival (HRGrimAge = 1.47 [1.40, 1.54] with p = 1.08 × 10-52, and HRbAge = 1.52 [1.44, 1.59] with p = 2.20 × 10-60). Finally, we introduce MethylBrowsR, an online tool to visualise epigenome-wide CpG-age associations.ConclusionsThe integration of multiple large datasets, EpiScores, non-linear DNAm effects, and new approaches to feature selection has facilitated improvements to the blood-based epigenetic prediction of biological and chronological age.

Project description:BACKGROUND:The number of nonagenarian cancer patients (? 90?years) is continuously increasing, and radiotherapy is performed in a relevant proportion of patients, as surgery and chemotherapy are often not feasible for these patients. However, the evidence regarding the feasibility and treatment outcomes after radiotherapy for this patient group is very limited. METHODS:All nonagenarian patients receiving (chemo) radiotherapy between 2009 and 2019 at the University of Freiburg - Medical Center were analyzed for patterns of care, overall survival (OS) and therapy-associated toxicities according to the Common Terminology Criteria for Adverse Events. Uni- and multivariate Cox regression analyses were conducted to assess the influence of patient- and treatment-related factors on patient outcomes. RESULTS:One hundred nineteen patients with a total of 137 irradiated lesions were included in this analysis. After a median follow-up of 27?months, median OS was 10?months with a 3-year OS amounting to 11.1%. Univariate analyses demonstrated that a reduced performance status (HR?=?1.56, 95% CI 1.00-2.45, p?<?0.05), a higher burden of comorbidities (HR?=?2.00, 95% CI 1.00-4.10, p?<?0.05) and higher UICC tumor stages (HR?=?2.21, 95% CI 1.14-4.26, p <?0.05) were associated with impaired survival rates. Split-course treatments (HR?=?2.05, 95% CI 1.07-3.94, p?<?0.05), non-completion of radiotherapy (HR?=?7.17, 95% CI 3.88-13.26, p?<?0.001) and palliative treatments (HR?=?2.84, 95% CI 1.68-4.81, p?<?0.05) were found to result in significantly reduced OS. In the multivariate analysis, split-course concepts (HR?=?2.21, 95% CI 1.10-4.37, p <?0.05) and palliative treatments (HR?=?3.19, 95% CI 1.77-5.75, p <?0.001) significantly deteriorated outcomes, while impaired ECOG status (HR?=?1.49, 95% CI 0.91-2.43, p =?0.11) did not. The vast majority of patients reported either no (n?=?40; 33.6%) or grade 1-2 acute toxicities (n?=?66; 55.5%), and only very few higher-grade toxicities were observed in our study. CONCLUSION:Radiotherapy for nonagenarian patients is generally feasible and associated with a low toxicity profile. Given the relatively poor OS rates and the importance of the quality of life for this patient group, individualized treatment regimens including hypofractionation concepts should be considered.

Dataset Information

Morphometric skin characteristics dependent on chronological and biological age: the Leiden Longevity Study.

Publications

Morphometric skin characteristics dependent on chronological and biological age: the Leiden Longevity Study.

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