新たに同定されたバイオマーカーにより、血液検査で早期の認知機能低下を検出できる可能性(Newly identified biomarkers may detect early cognitive decline via blood test)

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2023-11-28 ペンシルベニア州立大学(PennState)

◆極端なストレス要因に晒された人々の中で、精神障害や幼少期の虐待が引き起こす健康問題に加え、認知機能の低下を予測する遺伝的指標が特定された。ペンシルベニア州立大学の研究者は、この成果を「Neurobiology of Stress」に発表し、加速生物学的老化と認知機能低下の関連を明らかにし、早期の認知機能低下を予測する血液検査や個別化治療法の可能性を示唆している。
◆研究では、異なるデータセットで異なる遺伝的指標が使用され、認知機能低下との関連が示されたが、研究者はデザインの違いや年齢制約などを考慮して異なる結果が出た可能性を指摘している。

<関連情報>

エピジェネティックな年齢加速は、早期の人生における逆境や精神疾患に伴う成人期の認知能力低下のバイオマーカーとなる Epigenetic age acceleration as a biomarker for impaired cognitive abilities in adulthood following early life adversity and psychiatric disorders

John M. Felt, Natan Yusupov, Karra D. Harrington, Julia Fietz, Zhenyu “Zach” Zhang, Martin J. Sliwinski, Nilam Ram, Kieran J. O’Donnell, BeCOME Working Group, Michael J. Meaney, Frank W. Putnam, Jennie G. Noll, Elisabeth B. Binder, Chad E. Shenk
Neurobiology of Stress  Available online: 15 October 2023
DOI:https://doi.org/10.1016/j.ynstr.2023.100577

Fig. 1

Abstract

Background
Early life adversity and psychiatric disorders are associated with earlier declines in neurocognitive abilities during adulthood. These declines may be preceded by changes in biological aging, specifically epigenetic age acceleration, providing an opportunity to uncover genome-wide biomarkers that identify individuals most likely to benefit from early screening and prevention.

Methods
Five unique epigenetic age acceleration clocks derived from peripheral blood were examined in relation to latent variables of general and speeded cognitive abilities across two independent cohorts: 1) the Female Growth and Development Study (FGDS; n = 86), a 30-year prospective cohort study of substantiated child sexual abuse and non-abused controls, and 2) the Biological Classification of Mental Disorders study (BeCOME; n = 313), an adult community cohort established based on psychiatric disorders.

Results
A faster pace of biological aging (DunedinPoAm) was associated with lower general cognitive abilities in both cohorts and slower speeded abilities in the BeCOME cohort. Acceleration in the Horvath clock was significantly associated with slower speeded abilities in the BeCOME cohort but not the FGDS. Acceleration in the Hannum clock and the GrimAge clock were not significantly associated with either cognitive ability. Accelerated PhenoAge was associated with slower speeded abilities in the FGDS but not the BeCOME cohort.

Conclusions
The present results suggest that epigenetic age acceleration has the potential to serve as a biomarker for neurocognitive decline in adults with a history of early life adversity or psychiatric disorders. Estimates of epigenetic aging may identify adults at risk of cognitive decline that could benefit from early neurocognitive screening.

小児期の性的虐待に暴露された女性の発達の30年間にわたるコルチゾールの軌跡を前向きに測定: 中年期におけるエピジェネティックな年齢加速による調整 Cortisol trajectories measured prospectively across thirty years of female development following exposure to childhood sexual abuse: Moderation by epigenetic age acceleration at midlife

Chad E. Shenk, John M. Felt, Nilam Ram, Kieran J. O’Donnell, Martin J. Sliwinski, Irina Pokhvisneva, Lizbeth Benson, Michael J. Meaney, Frank W. Putnam, Jennie G. Noll
Psychoneuroendocrinology  Available online 26 November 2021
DOI:https://doi.org/10.1016/j.psyneuen.2021.105606

Abstract

Lasting changes in the hypothalamic-pituitary-adrenal (HPA) axis are a potential indication of the biological embedding of early life adversity, yet, prospective and repeatedly collected data are needed to confirm this relation. Likewise, integrating information from multiple biological systems, such as the HPA axis and the epigenome, has the potential to identify individuals with enhanced embedding of early life adversity. The current study reports results from the Female Growth and Development Study, a 30-year prospective cohort study of childhood sexual abuse (CSA). Females exposed to substantiated CSA and a demographically-similar comparison condition were enrolled and resting state cortisol concentrations were sampled on seven subsequent occasions across childhood, adolescence, and adulthood. Differences in participants’ cortisol trajectories were examined in relation to prior CSA exposure and DNA methylation-derived epigenetic age acceleration at midlife. Bilinear spline growth models revealed a trajectory where cortisol secretion increased until approximately age twenty and then declined into mid-life, consistent with normative trends. However, cortisol concentrations peaked at a lower level and transitioned to the decline phase at an earlier age for females in the CSA condition with increased epigenetic age acceleration. Robustness tests across three independent measures of epigenetic age acceleration demonstrated similar results for lower peak cortisol levels and earlier ages at transition. Results suggest that CSA is associated with significant changes in HPA-axis activity over extended periods of time with these changes most pronounced in females with accelerated epigenetic aging in mid-life. Implications for biological embedding models of early life adversity and adulthood health are discussed.

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