ArticlePloS one2008
Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging Xpd mice.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Inflammation and aging: signaling pathways and intervention therapies.Signal transduction and targeted therapy · 2023Review
- Biomarkers of aging.Science China. Life sciences · 2023Review
- Role of microRNA-122 in hepatic lipid metabolism of the weanling female rat offspring exposed to prenatal and postnatal caloric restriction.The Journal of nutritional biochemistry · 2019Article
- Apoptosis in the aging liver.Oncotarget · 2017Review
- GTF2E2 Mutations Destabilize the General Transcription Factor Complex TFIIE in Individuals with DNA Repair-Proficient Trichothiodystrophy.American journal of human genetics · 2016Article
- Controlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing.Nature communications · 2015Article
- NRMT1 knockout mice exhibit phenotypes associated with impaired DNA repair and premature aging.Mechanisms of ageing and development · 2015Article
- Oxidative and energy metabolism as potential clues for clinical heterogeneity in nucleotide excision repair disorders.The Journal of investigative dermatology · 2015Review
- BACH2: a marker of DNA damage and ageing.DNA repair · 2013Article
- Age-related skeletal dynamics and decrease in bone strength in DNA repair deficient male trichothiodystrophy mice.PloS one · 2012Article
- Metabolism, genomics, and DNA repair in the mouse aging liver.Current gerontology and geriatrics research · 2011Article
- Metal oxide nanoparticles interact with immune cells and activate different cellular responses.International journal of nanomedicineArticle
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
Abstract
Unrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. Xpd(TTD) mice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W), display severe symptoms of premature aging but have a reduced incidence of cancer. To gain further insight into the molecular basis of the mutant-specific manifestation of age-related phenotypes, we used comparative microarray analysis of young and old female livers to discover gene expression signatures distinguishing Xpd(TTD) mice from their age-matched wild type controls. We found a transcription signature of increased apoptosis in the Xpd(TTD) mice, which was confirmed by in situ immunohistochemical analysis and found to be accompanied by increased proliferation. However, apoptosis rate exceeded the rate of proliferation, resulting in homeostatic imbalance. Interestingly, a metabolic response signature was observed involving decreased energy metabolism and reduced IGF-1 signaling, a major modulator of life span. We conclude that while the increased apoptotic response to endogenous DNA damage contributes to the accelerated aging phenotypes and the reduced cancer incidence observed in the Xpd(TTD) mice, the signature of reduced energy metabolism is likely to reflect a compensatory adjustment to limit the increased genotoxic stress in these mutants. These results support a general model for premature aging in DNA repair deficient mice based on cellular responses to DNA damage that impair normal tissue homeostasis.
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