Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA; Medical Research Scholar Program, National Institutes of Health, Bethesda, Maryland, USA.
J Invest Dermatol. 2021 Apr;141(4S):976-984. doi: 10.1016/j.jid.2020.11.012. Epub 2021 Jan 9.
Aging results from intrinsic changes (chronologic) and damage from external exposures (extrinsic) on the human body. The skin is ideal to visually differentiate their unique features. Inherited diseases of DNA repair, such as xeroderma pigmentosum (XP), provide an excellent model for human aging due to the accelerated accumulation of DNA damage. Poikiloderma, atypical lentigines, and skin cancers, the primary cutaneous features of XP, occur in the general population but at a much older age. Patients with XP also exhibit ocular changes secondary to premature photoaging, including ocular surface tumors and pterygium. Internal manifestations of premature aging, including peripheral neuropathy, progressive sensorineural hearing loss, and neurodegeneration, are reported in 25% of patients with XP. Internal malignancies, such as lung cancer, CNS tumors, and leukemia and/or lymphoma, occur at a younger age in patients with XP, as do thyroid nodules. Premature ovarian failure is overrepresented among females with XP, occurring 20 years earlier than in the general population. Taken together, these clinical findings highlight the importance of DNA repair in maintaining genomic integrity. XP is a unique model of human premature aging, which is revealing new insights into aging mechanisms.
衰老是由人体内在变化（时间相关）和外部暴露引起的损伤（外在）造成的。皮肤是理想的，可以直观地区分其独特的特征。由于 DNA 损伤的加速积累，DNA 修复的遗传性疾病，如着色性干皮病（XP），为人类衰老提供了一个极好的模型。皮肤 XP 的主要特征是斑驳皮肤、非典型性色素斑和皮肤癌，这些在普通人群中也会出现，但年龄要大得多。XP 患者还会因过早光老化而出现眼部变化，包括眼表面肿瘤和翼状胬肉。25%的 XP 患者还会出现外周神经病变、进行性感觉神经性听力损失和神经退行性变等过早衰老的内部表现。肺癌、中枢神经系统肿瘤、白血病和/或淋巴瘤等内部恶性肿瘤以及甲状腺结节在 XP 患者中出现的年龄也较小。XP 女性中卵巢早衰的比例过高，比普通人群早 20 年发生。综上所述，这些临床发现强调了 DNA 修复在维持基因组完整性方面的重要性。XP 是人类早衰的独特模型，为衰老机制提供了新的见解。
