Journal
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
Volume 63, Issue 3, Pages 219-231Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/63.3.219
Keywords
longevity; nucleotide excision repair; Snell dwarf; stress resistance; ultraviolet light
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Funding
- NIA NIH HHS [T32 AG000114, U19 AG023122-05, T32-AG000114, T32 AG000114-24, U19 AG023122, AG054624, R01 AG054624, AG023122] Funding Source: Medline
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Fibroblasts isolated from long-lived hypopituitary dwarf mice are resistant to many cell stresses, including ultraviolet (UV) light and methyl methane sulfonate (MMS), which induce cell death by producing DNA damage. Here we report that cells from Snell dwarf mice recover more rapidly than controls from the inhibition of RNA synthesis induced by UV damage. Recovery of messenger RNA (mRNA) synthesis in particular is more rapid in dwarf cells, suggesting enhanced repair of the actively transcribing genes in dwarf-derived cells. At early time points, there was no difference in the repair of cyclobutane pyrimidine dimers (CPD) or 6-4 photoproducts (6-4PP) in the whole genome, nor was there any significant difference in the repair of UV lesions in specific genes. However, at later time points we found that more lesions had been removed from the genome of dwarf-derived cells. We have also found that cells from dwarf mice express higher levels of the nucleotide excision repair proteins XPC and CSA, suggesting a causal link to enhanced DNA repair. Overall, these data suggest a mechanism for the UV resistance of Snell dwarf-derived fibroblasts that could contribute to the delay of aging and neoplasia in these mice.
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