PML-nuclear bodies decrease with age and their stress response is impaired in aged individuals.
BACKGROUND
Promyelocytic leukemia nuclear bodies (PML-NBs) have been depicted as structures which are involved in processing cell damages and DNA double-strand break repairs. The study was designed to evaluate differences in patients' PML-NBs response to stress factors like a cancerous disease and ionizing radiation exposure dependent on age.


METHODS
In order to clarify the role of PML-NBs in the aging process, we examined peripheral blood monocytes of 134 cancer patients and 41 healthy individuals between 22 and 92 years of age, both before and after in vitro irradiation. Additionally, we analyzed the samples of the cancer patients after in vivo irradiation. Cells were immunostained and about 1600 cells per individual were analyzed for the presence of PML- and γH2AX foci.


RESULTS
The number of existing PML-NBs per nucleus declined with age, while the number of γH2AX foci increased with age. There was a non-significant trend that in vivo irradiation increased the number of PML-NBs in cells of young study participants, while in older individuals PML-NBs tended to decrease. It can be assumed that PML-NBs decrease in number during the process of aging.


CONCLUSIONS
The findings suggest that there is a dysfunctional PML-NBs stress response in aged cells.
Barbara
B
Wenger
Manuela
M
Schwegler
Maria
M
Brunner
Christoph
C
Daniel
Manfred
M
Schmidt
Rainer
R
Fietkau
Department of Radiation Oncology, University Hospitals and Friedrich-Alexander-University Erlangen-Nürnberg, Universitätsstraße 27, D-91054 Erlangen, Germany. Luitpold.Distel@uk-erlangen.de.
Luitpold V
LV
Distel
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D000071156:Promyelocytic Leukemia Protein; D011446:Prospective Studies; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D055815:Young Adult
D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human