a Dipartimento di Biologia e Biotecnologie "C. Darwin" , Sapienza Università di Roma , Roma , Italy.
b Istituto di Biologia e Patologia Molecolari del CNR , Rome , Italy.
Nucleus. 2018 Dec 31;9(1):368-379. doi: 10.1080/19491034.2018.1476793. Epub 2018 Jun 23.
Progeroid syndromes induced by mutations in lamin A or in its interactors - named progeroid laminopathies - are model systems for the dissection of the molecular pathways causing physiological and premature aging. A large amount of data, based mainly on the Hutchinson Gilford Progeria syndrome (HGPS), one of the best characterized progeroid laminopathy, has highlighted the role of lamins in multiple DNA activities, including replication, repair, chromatin organization and telomere function. On the other hand, the phenotypes generated by mutations affecting genes directly acting on DNA function, as mutations in the helicases WRN and BLM or in the polymerase polδ, share many of the traits of progeroid laminopathies. These evidences support the hypothesis of a concerted implication of DNA function and lamins in aging. We focus here on these aspects to contribute to the comprehension of the driving forces acting in progeroid syndromes and premature aging.
由核纤层蛋白 A 或其相互作用蛋白突变引起的早衰综合征——称为早衰性核纤层病——是解析导致生理和过早衰老的分子途径的模型系统。大量数据主要基于亨廷顿吉尔福德早衰综合征（HGPS），这是最具特征性的早衰性核纤层病之一，强调了核纤层蛋白在多种 DNA 活性中的作用，包括复制、修复、染色质组织和端粒功能。另一方面，直接影响 DNA 功能的基因突变引起的表型，如解旋酶 WRN 和 BLM 或聚合酶 polδ 的突变，与早衰性核纤层病有许多共同的特征。这些证据支持 DNA 功能和核纤层蛋白在衰老中的协同作用假说。我们在这里重点关注这些方面，以帮助理解在早衰综合征和过早衰老中起作用的驱动力。
