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SUMMARY:Aging and cancer: The impact of DNA damage  - Prof. Jan Hoeijmaker
 s 
DTSTART:20140528T120000Z
DTEND:20140528T130000Z
UID:TALK51857@talks.cam.ac.uk
CONTACT:37370
DESCRIPTION:\nInherited defects in nucleotide excision repair (NER) removi
 ng helix-distorting DNA lesions are associated with cancer predisposition 
 in xeroderma pigmentosum and neurodevelopmental deficits and segmental pro
 geria in Cockayne syndrome and trichothiodystrophy (TTD). Mutations in sin
 gle NER genes\, such as XPD\, are linked with all three disorders. Various
  single and double NER mouse mutants reveal that the severity of specific 
 repair defects strictly correlates with the acceleration of selective prem
 ature aging features\, whereas the type of DNA repair defect determines th
 e kind of progeroid symptoms and/or cancer susceptibility. Microarray\, fu
 nctional and physiological studies revealed that persistent DNA damage\, l
 ike caloric restriction\, down-regulates the IGF1/GH-\, lacto- and thyrotr
 opic hormonal axes and upregulates anti-oxidant defenses\, favoring mainte
 nance at the expense of growth. This ‘survival response’ links accumul
 ation of DNA damage and IGF1 control of life span. Micro- and mRNA express
 ion profiling of normal\, accelerated and delayed aging also revealed a cl
 ear parallel with the expression changes triggered by persistent transcrip
 tion-blocking DNA lesions. These findings strongly support the DNA damage 
 theory of aging. We will present phenotypes of conditional DNA repair mode
 ls targeting aging to selected organs\, parallels with Alzheimer’s disea
 se and the effect of nutritional interventions on the life span of progero
 id repair mutants.\n\n\nIf you would like to attend this talk\, please con
 tact Handan Elaman in advance to arrange Babraham site access - Handan.Ela
 man@babraham.ac.uk    \n\n\n
LOCATION:The Babraham Institute Conference Centre
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