老化のバイオロジーに関するバイオマーカーを発見(Uncovering the Biology of Growing Old)

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2025-10-22 タフツ大学

タフツ大学とワシントン大学などの共同研究チームは、約800匹の犬を対象に加齢と代謝の関係を調べ、血中代謝物の約40%が年齢とともに変化することを発見した。特に「翻訳後修飾アミノ酸(ptmAAs)」と呼ばれる代謝物が、犬の年齢・性別・体格を問わず加齢と強く関連していた。これらは腸内細菌による生成やタンパク質分解の過程で生じるとされ、腎機能の低下によって血中に蓄積する傾向が確認された。研究者は、腎臓が老化の健康度に重要な役割を果たす可能性を指摘している。今後、同一個体を長期追跡して代謝物の変化を分析し、腸内細菌や筋肉量との関連を検証する予定。研究は「Dog Aging Project」の一環で行われ、犬の健康寿命だけでなく人間の老化機構解明にも資する成果として注目されている。論文は『Aging Cell』誌に掲載。

<関連情報>

血液中のタンパク質分解産物は老化生理学のバイオマーカーとなる:犬の老化プロジェクトの研究結果 Protein Catabolites as Blood-Based Biomarkers of Aging Physiology: Findings From the Dog Aging Project

Benjamin R. Harrison, Maria Partida-Aguilar, Abbey Marye, Danijel Djukovic, Mandy Kauffman, Matthew D. Dunbar, Blaise L. Mariner, Brianah M. McCoy, Yadid M. Algavi, Efrat Muller …
Aging Cell  Published: 22 October 2025
DOI:https://doi.org/10.1111/acel.70226

老化のバイオロジーに関するバイオマーカーを発見(Uncovering the Biology of Growing Old)

ABSTRACT

Our understanding of aging has grown through the study of systems biology, including single-cell analysis, proteomics and metabolomics. Studies in lab organisms in controlled environments, while powerful and complex, fall short of capturing the breadth of genetic and environmental variation in nature. Thus, there is now a major effort in geroscience to identify aging biomarkers that might be applied across the diversity of humans and other free-living species. To meet this challenge, the Dog Aging Project (DAP) aims to identify cross-sectional and longitudinal patterns of aging in complex systems, and how these are shaped by the diversity of genetic and environmental variation among companion dogs. Here we surveyed the plasma metabolome from the first year of sampling of the Precision Cohort of the DAP. By incorporating extensive metadata and whole genome sequencing, we overcome the limitations inherent in breed-based estimates of genetic effects, and probe the physiological basis of the age-related metabolome. We identified effects of age on approximately 36% of measured metabolites. We also discovered a novel biomarker of age in the post-translationally modified amino acids (ptmAAs). The ptmAAs, which are generated by protein hydrolysis, covaried both with age and with other biomarkers of amino acid metabolism, and in a way that was robust to diet. Clinical measures of kidney function mediated about half of the age effect on ptmAA levels. This work identifies ptmAAs as robust indicators of age in dogs, and points to kidney function as a physiological mediator of age-associated variation in the plasma metabolome.

医療・健康
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