Reduction of alkali-induced white blood cell DNA unwinding rate: a potential biomarker of aging.
The modification of DNA with aging or in diabetes mellitus has been proposed as a possible mechanism of cellular senescence. To test this hypothesis, we measured DNA strand breaks in human white blood cells (WBC) by fluorometric analysis of DNA unwinding in alkaline solutions. In a nondiabetic population with an age range 22-80 years, there was a significant negative correlation between the rate of DNA unwinding and the age of the individual with an r of 0.60 (p less than .001). The rate of alkaline digestion of double-stranded DNA (ds DNA) in the elderly diabetics (n = 26, 65-80 yrs) was significantly lower than that in the nondiabetic, age-matched ambulatory elderly. Within the healthy group studied, there was a statistically significant correlation between the rate of DNA unwinding and plasma glucose concentration (p less than .05) or glycosylated hemoglobin A1C levels (p less than .0001). The availability of WBC and the relative ease and rapidity of the technique employed make this a potentially useful biological marker of aging.
GRECC, VA Medical Center, Sepulveda.
J M
JM
Hartnell
J E
JE
Morley
A D
AD
Mooradian
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001786:Blood Glucose / Q000032:analysis; D002940:Circadian Rhythm; D004247:DNA; D004249:DNA Damage; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007962:Leukocytes / Q000378:metabolism; D008875:Middle Aged; D009690:Nucleic Acid Conformation; D013050:Spectrometry, Fluorescence
D001786:Blood Glucose; D005819:Genetic Markers; D004247:DNA