Laboratory of Integrative Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland.
Université de Lyon, Ecole Normale Supérieure de Lyon, Université de Lyon 1, CNRS, LGL-TPE, Lyon, France.
Nat Commun. 2022 Feb 1;13(1):607. doi: 10.1038/s41467-022-28060-x.
Organic elements make up 99% of an organism but without the remaining inorganic bioessential elements, termed the metallome, no life could be possible. The metallome is involved in all aspects of life, including charge balance and electrolytic activity, structure and conformation, signaling, acid-base buffering, electron and chemical group transfer, redox catalysis energy storage and biomineralization. Here, we report the evolution with age of the metallome and copper and zinc isotope compositions in five mouse organs. The aging metallome shows a conserved and reproducible fingerprint. By analyzing the metallome in tandem with the phenome, metabolome and proteome, we show networks of interactions that are organ-specific, age-dependent, isotopically-typified and that are associated with a wealth of clinical and molecular traits. We report that the copper isotope composition in liver is age-dependent, extending the existence of aging isotopic clocks beyond bulk organic elements. Furthermore, iron concentration and copper isotope composition relate to predictors of metabolic health, such as body fat percentage and maximum running capacity at the physiological level, and adipogenesis and OXPHOS at the biochemical level. Our results shed light on the metallome as an overlooked omic layer and open perspectives for potentially modulating cellular processes using careful and selective metallome manipulation.
有机元素构成了生物体的 99%，但如果没有其余的无机生物必需元素，即所谓的金属组，就不可能有生命存在。金属组参与了生命的各个方面，包括电荷平衡和电解质活性、结构和构象、信号传递、酸碱缓冲、电子和化学基团转移、氧化还原催化、能量储存和生物矿化。在这里，我们报告了五个小鼠器官的金属组以及铜和锌同位素组成随年龄的演变。老化的金属组表现出保守且可重复的特征。通过分析金属组与表型、代谢组和蛋白质组的关系，我们展示了特定于器官、年龄相关、同位素典型的相互作用网络，这些网络与大量的临床和分子特征相关。我们报告说，肝脏中的铜同位素组成随年龄而变化，这将衰老同位素时钟的存在扩展到了有机元素之外。此外，铁浓度和铜同位素组成与代谢健康的预测因素有关，例如体脂肪百分比和生理水平下的最大跑步能力，以及生化水平上的脂肪生成和 OXPHOS。我们的研究结果揭示了金属组作为一个被忽视的组学层，并为使用谨慎和选择性的金属组操作来潜在调节细胞过程开辟了新的视角。
