Mediterranean Institute for Life Sciences, Split, Croatia, Naos Institute for Life Sciences, Aix-en-Provence, France, Université R.-Descartes Paris-5, faculté de médecine, INSERM U1001, Paris, France.
Eur J Dermatol. 2019 Apr 1;29(S1):11-14. doi: 10.1684/ejd.2019.3534.
Ageing and age-related diseases (ARD) share a common biological clock that appears as their root cause: protein damage. A majority of proteins have evolved into native structures resistant to oxidative damage but any folding imperfections, including those due to "silent" amino acid substitutions, reduce oxidation resistance. Damaged proteins accumulate with age and trigger ageing-like phenotypes reversible by their turnover, while acquired genome alterations remain as stable consequences of protein malfunction. Ageing and ARD display species-specific latency in phenotypic expression. Disease latency may be proposed as to be due to phenotypic suppression of cellular defects by molecular traffic among neighbouring cells. Such cross-complementation of functional deficiencies acts as a kind of tissue-based cellular "solidarity", called cellular parabiosis. Chronic inflammation reveals dormant cell phenotypes and shortens disease latency by the breakdown of cell-cell communication, as in tumour promotion and inflammation. At the present time, predictive diagnostics, prognostics, prevention and even cure of disease by phenotypic reversion become conceivable.
衰老和与衰老相关的疾病 (ARD) 有着共同的生物钟，这似乎是它们的根本原因：蛋白质损伤。大多数蛋白质已经进化成具有抵抗氧化损伤的天然结构，但任何折叠缺陷，包括由于“沉默”氨基酸取代引起的缺陷，都会降低氧化抵抗能力。随着年龄的增长，受损的蛋白质会积累，并引发类似于衰老的表型，这些表型可以通过其周转率来逆转，而获得的基因组改变则作为蛋白质功能障碍的稳定后果保留下来。衰老和 ARD 在表型表达上表现出特定物种的潜伏期。疾病潜伏期可能是由于细胞缺陷的表型受到邻近细胞之间的分子运输的抑制。这种功能缺陷的交叉互补作用表现为一种组织为基础的细胞“团结”，称为细胞共生。慢性炎症通过破坏细胞间的通讯揭示休眠细胞表型，并缩短疾病潜伏期，就像在肿瘤促进和炎症中一样。目前，通过表型逆转进行疾病的预测诊断、预后、预防甚至治疗变得可以想象。
