INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302/EMR6001, Nantes Université, Nantes, France.
NAOS-ILS, Aix-en-Provence, France.
Eur J Dermatol. 2024 Aug 1;34(4):355-360. doi: 10.1684/ejd.2024.4739.
Skin aging is associated with a progressive decline in physiological functions, skin cancers and, ultimately, death. It may be categorized as intrinsic or extrinsic, whereby intrinsic aging is attributed to chronological and genetic factors. At the molecular level, skin aging involves changes in protein conformation and function. The skin proteome changes constantly, mainly through carbonylation; an irreversible phenomenon leading to protein accumulation as toxic aggregates that impair cellular physiology and accelerate skin aging. This review details the central role of proteostasis during skin aging and why proteome protection may be a promising approach in mitigating skin aging. A comprehensive literature review of 87 articles focusing on the proteome, proteostasis, proteotoxicity, protein carbonylation, and the impact of the damaged proteome on aging, and in particular skin aging, was conducted. Skin aging is associated with deficiencies in the repair mechanisms of DNA, transcriptional control, mitochondrial function, cell cycle control, apoptosis, cellular metabolism, changes in hormonal levels secondary to toxicity of damaged proteins, and cell-to-cell communication for tissue homeostasis, which are largely controlled by proteins. In this context, a damaged proteome that leads to the loss of proteostasis may be considered as the first step in tissue aging. There is growing evidence that a healthy proteome plays a central role in skin and in maintaining healthy tissues, thus slowing down the process of skin aging. Hence, protecting the proteome against oxidative or other damage may be an appropriate strategy to prevent and delay skin aging.
皮肤衰老与生理功能的逐渐下降、皮肤癌，最终是死亡有关。它可以分为内在的或外在的，内在的衰老归因于时间和遗传因素。在分子水平上，皮肤衰老涉及蛋白质构象和功能的变化。皮肤蛋白质组不断变化，主要通过羰基化作用；这是一种导致蛋白质积累的不可逆现象，形成有毒聚集体，损害细胞生理功能并加速皮肤衰老。这篇综述详细介绍了皮肤衰老过程中蛋白质稳态的核心作用，以及为什么保护蛋白质组可能是减轻皮肤衰老的一种有前途的方法。对 87 篇重点关注蛋白质组、蛋白质稳态、蛋白毒性、蛋白质羰基化以及受损蛋白质组对衰老，特别是皮肤衰老的影响的文献进行了全面综述。皮肤衰老与 DNA 修复机制、转录控制、线粒体功能、细胞周期控制、细胞凋亡、细胞代谢、毒性蛋白引起的激素水平变化以及组织内稳态的细胞间通讯缺陷有关，这些主要由蛋白质控制。在这种情况下，导致蛋白质稳态丧失的受损蛋白质组可能被认为是组织衰老的第一步。越来越多的证据表明，健康的蛋白质组在皮肤和维持健康组织中起着核心作用，从而减缓皮肤衰老的过程。因此，保护蛋白质组免受氧化或其他损伤可能是预防和延缓皮肤衰老的适当策略。
