2023-02-22 ミシガン大学
◆ISRの調査研究センター准教授Jessica Faulと南カリフォルニア大学老年学教授Eileen Crimminsは、DNAメチル化など、ヒトゲノムのエピジェネティックな変化を調べることで、将来の健康状態を予測できる可能性があることを発見しました。
◆メチル化は、遺伝子が時間と共に制御されるプロセスです。FaulとCrimminsによる新しい研究は、メチル化の追跡が、生物学的年齢の加速を測定するのに役立つことを示唆しています。これまでの研究では、老化の速度に関する要約的な指標を検討してきましたが、その多くは小規模なサンプルに適用されたものでした。このプロジェクトでは、米国人口の代表的な大規模サンプルを調査しており、研究から得られた結論を強化しています。
◆研究者達は、年齢中央値68歳の成人参加者3,581人のデータを分析して、加齢に関連した健康アウトカムに対する彼らのモデルの予測能力を評価しました。
<関連情報>
- https://news.umich.edu/new-research-highlights-dna-methylation-as-noteworthy-biomarker-for-epigenetic-aging/
- https://www.pnas.org/doi/10.1073/pnas.2215840120
代表的な高齢者サンプルにおけるエピジェネティックな加齢加速。加齢に伴う疾病および死亡率との関連性 Epigenetic-based age acceleration in a representative sample of older Americans: Associations with aging-related morbidity and mortality
Jessica D. Faul,Jung Ki Kim,Morgan E. Levine,Bharat Thyagarajan,David R. Weir,Eileen M. Crimmins
Proceedings of the National Academy of Sciences Published:February 21, 2023
DOI:https://doi.org/10.1073/pnas.2215840120
Significance
In a nationally representative US adult population, measures of epigenetic age acceleration are associated with concurrent cognitive dysfunction, functional limitations and chronic conditions measured 2 y after DNA methylation measurement, and 4-y mortality. PC-based clocks do not significantly change the relationship between DNAm-based age acceleration and health outcomes. These findings suggest that along with demographic measures, SES, mental health, and health behaviors, epigenetic age acceleration serves as a useful tool to facilitate investigation into the biology of aging and helps in the prediction of later life morbidity and mortality.
Abstract
Biomarkers developed from DNA methylation (DNAm) data are of growing interest as predictors of health outcomes and mortality in older populations. However, it is unknown how epigenetic aging fits within the context of known socioeconomic and behavioral associations with aging-related health outcomes in a large, population-based, and diverse sample. This study uses data from a representative, panel study of US older adults to examine the relationship between DNAm-based age acceleration measures in the prediction of cross-sectional and longitudinal health outcomes and mortality. We examine whether recent improvements to these scores, using principal component (PC)-based measures designed to remove some of the technical noise and unreliability in measurement, improve the predictive capability of these measures. We also examine how well DNAm-based measures perform against well-known predictors of health outcomes such as demographics, SES, and health behaviors. In our sample, age acceleration calculated using “second and third generation clocks,” PhenoAge, GrimAge, and DunedinPACE, is consistently a significant predictor of health outcomes including cross-sectional cognitive dysfunction, functional limitations and chronic conditions assessed 2 y after DNAm measurement, and 4-y mortality. PC-based epigenetic age acceleration measures do not significantly change the relationship of DNAm-based age acceleration measures to health outcomes or mortality compared to earlier versions of these measures. While the usefulness of DNAm-based age acceleration as a predictor of later life health outcomes is quite clear, other factors such as demographics, SES, mental health, and health behaviors remain equally, if not more robust, predictors of later life outcomes.
