Barbouti Alexandra, Lagopati Nefeli, Veroutis Dimitris, Goulas Vlasios, Evangelou Konstantinos, Kanavaros Panagiotis, Gorgoulis Vassilis G, Galaris Dimitrios
Department of Anatomy-Histology-Embryology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.
Laboratory of Histology-Embryology, Molecular Carcinogenesis Group, Faculty of Medicine, School of Health Science, National and Kapodistrian University of Athens, 75, Mikras Asias Str., Goudi, 11527 Athens, Greece.
Antioxidants (Basel). 2021 Mar 21;10(3):491. doi: 10.3390/antiox10030491.
One of the prevailing perceptions regarding the ageing of cells and organisms is the intracellular gradual accumulation of oxidatively damaged macromolecules, leading to the decline of cell and organ function (free radical theory of ageing). This chemically undefined material known as "lipofuscin," "ceroid," or "age pigment" is mainly formed through unregulated and nonspecific oxidative modifications of cellular macromolecules that are induced by highly reactive free radicals. A necessary precondition for reactive free radical generation and lipofuscin formation is the intracellular availability of ferrous iron (Fe) ("labile iron"), catalyzing the conversion of weak oxidants such as peroxides, to extremely reactive ones like hydroxyl (HO) or alcoxyl (RO) radicals. If the oxidized materials remain unrepaired for extended periods of time, they can be further oxidized to generate ultimate over-oxidized products that are unable to be repaired, degraded, or exocytosed by the relevant cellular systems. Additionally, over-oxidized materials might inactivate cellular protection and repair mechanisms, thus allowing for futile cycles of increasingly rapid lipofuscin accumulation. In this review paper, we present evidence that the modulation of the labile iron pool distribution by nutritional or pharmacological means represents a hitherto unappreciated target for hampering lipofuscin accumulation and cellular ageing.
关于细胞和生物体衰老的一个普遍观点是，细胞内氧化损伤的大分子逐渐积累，导致细胞和器官功能衰退（衰老的自由基理论）。这种化学性质不明确的物质被称为“脂褐素”“类蜡质”或“老年色素”，主要是由高活性自由基诱导的细胞大分子的无规律、非特异性氧化修饰形成的。活性自由基产生和脂褐素形成的一个必要前提是细胞内亚铁（Fe）（“不稳定铁”）的存在，它催化过氧化物等弱氧化剂转化为极具活性的羟基（HO）或烷氧基（RO）自由基。如果氧化后的物质长时间未得到修复，它们可能会进一步氧化生成最终的过度氧化产物，这些产物无法被相关细胞系统修复、降解或胞吐。此外，过度氧化的物质可能会使细胞保护和修复机制失活，从而导致脂褐素积累越来越快的无效循环。在这篇综述论文中，我们提供证据表明，通过营养或药理学手段调节不稳定铁池的分布是一个迄今为止未被重视的阻碍脂褐素积累和细胞衰老的靶点。
