Background:Physical activity(PA)has substantial health benefits and is important in combatting chronic diseases,which have been associated with ele-vated levels of advanced glycation endproducts(AGEs).AGEs play a role in the aging process,and an association between PA and AGEs has been reported.We aimed to investigate the relationship between PA and AGE accumulation in a general population and in a population with chronic diseases.Methods:This large cross-sectional population study used data from adult participants in the LifeLines project,with participant information drawn from the LifeLines database as well data from patients with diabetes mellitus or renal and/or cardiovascular diseases.Tissue AGE accumulation was assessed non-invasively by skin-autofluorescence(SAF)using an AGE reader(DiagnOptics Technologies BV,Groningen,the Netherlands).PA was assessed using the short questionnaire to assess health-enhancing physical activity(SQUASH).Multivariate linear regression analyses were adjusted for age,body mass index,sex,and smoking status.Results:Data from 63,452 participants(general population n=59,177,chronic disease n=4275)were analyzed.The general population was signifi-cantly younger(43.58±11.77 years,mean±SD)and had significantly lower SAF(1.90±0.42 arbitrary units(AU))compared to the population with chronic disease(age:55.51±12.07 years;SAF:2.27±0.51 AU).In the group with chronic disease,more hours of moderate to vigorous physical activities per week were associated with lower SAF(β=-0.002,95％confidence interval(95％CI):-0.002 to-0.001).For the general population,there was no association between hours of moderate to vigorous activity and SAF(β=3.2×10-5,95％CI:0.000-0.001,p=0.742).However,there was an association in the general population between total hours of PA per week and SAF(β=4.2×10-4,95％CI:0.000-0.001,p＜0.001),but this association was not found in the chronic disease population(β=-3.2×10-4,95％CI:-0.001 to 0.000,p=0.347).Conclusion:Our study demonstrates that an inverse relationship exists between PA and AGE accumulation in the population with chronic disease.More hours of moderate to vigorous activity is associated with a significantly decreased SAF.More PA is associated with a lower SAF,even after adjusting for the established predictors(age,body mass index,smoking status,and sex).Our findings could help to promote health and prolong longevity.