The burden of overweight: Higher body mass index, but not vital exhaustion, is associated with higher DNA damage and lower DNA repair capacity.

BACKGROUND/OBJECTIVES: DNA damage and the capacity to repair damaged DNA have been associated with the pathogenesis of several diseases such as cancer. While it is well known that external mutagenic agents can induce DNA damage, less is known about endogenous contributors to genomic instability. The aim of this study was to investigate whether excess body weight as a physiological factor and vital exhaustion as a psychological factor would be associated with basal levels of DNA damage as well as DNA repair capacity.

SUBJECTS/METHODS: In a cross-sectional between-subject design we recruited 53 apparently healthy men within the normal to non-obese overweight range (mean BMI: 25.2 ± 0.5) who were either vitally exhausted (VE) (VE-score ≥ 10) or non-exhausted (VE-score ≤ 3). Vital exhaustion was assessed using the Maastricht Vital Exhaustion Questionnaire. We assessed DNA damage and repair in terms of strand breaks in PBMCs by means of the automated Fluorimetric Detection of Alkaline Unwinding (FADU) assay. DNA repair capacity was assessed by repeatedly measuring the amount of intact DNA up to 90 min after standardized X-irradiation of the cells.

RESULTS

General linear models revealed that elevated levels of basal DNA damage (β=-0.34, p=0.013, f=0.33) as well as impaired capacity to repair damaged DNA (F(1/50)=5.40, p=0.024, f=0.33) with increasing BMI, but not with vital exhaustion (p's ≥ 0.63).

CONCLUSION

Our findings point to DNA integrity impairments with increasing BMI, already in the overweight range, and suggest impaired DNA repair as a potential underlying molecular mechanism. In contrast, the psychological factor vital exhaustion was not associated with DNA damage or DNA repair capacity.