Clinical implications of the basic defects in Cockayne syndrome and xeroderma pigmentosum and the DNA lesions responsible for cancer, neurodegeneration and aging

• Published in: Mechanisms of ageing and development 2008-07, Vol.129 (7), p.492-497
• Main Authors: Cleaver, J.E., Revet, I.
• Format: Article
• Language: English
• Subjects: Aging; Aging - genetics; Animals; Cockayne Syndrome - diagnosis; Cockayne Syndrome - drug therapy; Cockayne Syndrome - genetics; DNA Damage; DNA Repair; Humans; Mice; Neoplasms - genetics; Neurodegeneration; Neurodegenerative Diseases - genetics; Purkinje cells; Reactive oxygen; Transcription coupled repair; Xeroderma Pigmentosum - diagnosis; Xeroderma Pigmentosum - drug therapy; Xeroderma Pigmentosum - genetics
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2008.01.005

Cancer, aging, and neurodegeneration are all associated with DNA damage and repair in complex fashions. Aging appears to be a cell and tissue-wide process linked to the insulin-dependent pathway in several DNA repair deficient disorders, especially in mice. Cancer and neurodegeneration appear to have complementary relationships to DNA damage and repair. Cancer arises from surviving cells, or even stem cells, that have down-regulated many pathways, including apoptosis, that regulate genomic stability in a multi-step process. Neurodegeneration however occurs in nondividing neurons in which the persistence of apoptosis in response to reactive oxygen species is, itself, pathological. Questions that remain open concern: sources and chemical nature of naturally occurring DNA damaging agents, especially whether mitochondria are the true source; the target tissues for DNA damage and repair; do the human DNA repair deficient diseases delineate specific pathways of DNA damage relevant to clinical outcomes; if naturally occurring reactive oxygen species are pathological in human repair deficient disease, would anti-oxidants or anti-apoptotic agents be feasible therapeutic agent?