DNA methylation (DNAm) clocks hold promise for measuring biological age, useful for guiding clinical interventions and forensic identification. This study compared the commonly used DNAm clocks, using DNA methylation and SNP data generated from nearly 1000 human blood or buccal swab samples. We evaluated different preprocessing methods for age estimation, investigated the association of epigenetic age acceleration (EAA) with various lifestyle and sociodemographic factors, and undertook a series of novel genome-wide association analyses for different EAA measures to find associated genetic variants. Our results highlighted the Skin&Blood clock with ssNoob normalization as the most accurate predictor of chronological age. We provided novel evidence for an association between the practice of yoga and a reduction in the pace of aging (DunedinPACE). Increased sleep and physical activity were associated with lower mortality risk score (MRS) in our dataset. University degree, vegetable consumption, and coffee intake were associated with reduced levels of epigenetic aging, whereas smoking, higher BMI, meat consumption, and manual occupation correlated well with faster epigenetic aging, with FitAge, GrimAge, and DunedinPACE clocks showing the most robust associations. In addition, we found a novel association signal for SOCS2 rs73218878 (p = 2.87 × 10) and accelerated GrimAge. Our study emphasizes the importance of an optimized DNAm analysis workflow for accurate estimation of epigenetic age, which may influence downstream analyses. The results support the influence of genetic background on EAA. The associated SOCS2 is a member of the suppressor of cytokine signaling family known for its role in human longevity. The reported association between various risk factors and EAA has practical implications for the development of health programs to improve quality of life and reduce premature mortality associated with age-related diseases.
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http://dx.doi.org/10.1007/s11357-023-01029-4 | DOI Listing |
Nat Rev Genet
January 2025
Institute of Ecology and Evolution, University of Oregon, Eugene, OR, USA.
Traditionally, differences among individuals have been divided into genetic and environmental causes. However, both types of variation can underlie regulatory changes in gene expression - that is, epigenetic changes - that persist across cell divisions (developmental differentiation) and even across generations (transgenerational inheritance). Increasingly, epigenetic variation among individuals is recognized as an important factor in human diseases and ageing.
View Article and Find Full Text PDFExp Hematol
January 2025
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin, China.. Electronic address:
Hematopoietic stem cells (HSCs) are central to blood formation and play a pivotal role in hematopoietic and systemic aging. With aging, HSCs undergo significant functional changes, such as an increased stem cell pool, declined homing and reconstitution capacity, and skewed differentiation towards myeloid and megakaryocyte/platelet progenitors. These phenotypic alterations are likely due to the expansion of certain clones, known as clonal hematopoiesis (CH), which leads to disrupted hematopoietic homeostasis, including anemia, impaired immunity, higher risks of hematological malignancies, and even associations with cardiovascular disease, highlighting the broader impact of HSC aging on overall health.
View Article and Find Full Text PDFStem Cell Rev Rep
January 2025
Department of Integrative Biology, Gene Therapy Laboratory, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, TN, 632 014, India.
Hematopoietic stem cells are a unique population of tissue-resident multipotent cells with an extensive ability to self-renew and regenerate the entire lineage of differentiated blood cells. Stem cells reside in a highly specialized microenvironment with surrounding supporting cells, forming a complex and dynamic network to preserve and maintain their function. The survival, activation, and quiescence of stem cells are largely influenced by niche-derived signals, with aging niche contributing to a decline in stem cell function.
View Article and Find Full Text PDFAging Cell
January 2025
Department of Biobehavioral Health, Penn State University, University Park, Pennsylvania, USA.
Epigenetic clocks are a common group of tools used to measure biological aging-the progressive deterioration of cells, tissues, and organs. Epigenetic clocks have been trained almost exclusively using blood-based tissues, but there is growing interest in estimating epigenetic age using less-invasive oral-based tissues (i.e.
View Article and Find Full Text PDFAging Med (Milton)
December 2024
Department of Laboratory Medicine The Second Xiangya Hospital, Central South University Changsha Hunan China.
Objectives: To investigate the effects of suberoylanilide hydroxamic acid (SAHA) on lung fibroblast activation and to examine the role of p66Shc in this process.
Methods: An in vitro pulmonary fibrosis model was established using transforming growth factor-β (TGF-β)-induced MRC-5 lung fibroblasts. The proliferation and migration capacities of MRC-5 cells, along with the expression of fibrosis-related genes, were assessed following treatment with SAHA and/or silence of p66Shc.
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