Homocysteine and inflammation as main determinants of oxidative stress in the elderly.
Oxidative stress is commonly observed in the elderly and could be involved in age-related diseases. However, the determinants of superoxide anion overproduction are not clearly understood. Superoxide anion production was evaluated using a lucigenin-based chemiluminescence method in 478 elderly subjects (304 women, 174 men; 79.5+/-7.1 years). Homocysteine (HCy) metabolism (homocysteinemia, vitamin B12, plasma, and erythrocyte folates), inflammation (CRP, fibrinogen, alpha-1 acid glycoprotein), lipid parameters (total cholesterol, triglycerides, HDL and LDL cholesterol), and nutritional parameters (albumin, transthyretin) were determined. The results show that HCy levels (p<0.001) and superoxide anion production (p=0.04) increase with aging, but CRP does not. Highest HCy (>20 microM) (OR 1.83 (1.09-3.07), p=0.02) and CRP over 5 mg/L (adjusted OR 2.01 (1.15-3.51), p=0.01) are the main determinants in superoxide anion production in the elderly. These clinical data are confirmed in an in vitro study using THP-1 monocyte-like cells. Incubation with HCy thiolactone (HTL) (0-200 microM) and LPS (0-20 ng/ml) dramatically enhances NADPH oxidase expression and activation. Moreover, a synergic action was evidenced for low concentrations of HTL (20 microM) and LPS (5 ng). Taken together, the clinical data and in vitro experiments support the hypothesis that moderate homocysteinemia and low-grade inflammation synergically enhance NADPH oxidase activity in the elderly.
Ventura
Emilie
E
Biochemistry Department, Lapeyronie Hospital, CHU de Montpellier, 34295 Montpellier Cedex 5, France.
Durant
Richard
R
Jaussent
Audrey
A
Picot
Marie-Christine
MC
Morena
Marion
M
Badiou
Stéphanie
S
Dupuy
Anne-Marie
AM
Jeandel
Claude
C
Cristol
Jean-Paul
JP
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D002097:C-Reactive Protein / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006710:Homocysteine / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007249:Inflammation; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D015596:Nutrition Assessment; D018384:Oxidative Stress; D011228:Prealbumin / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D011228:Prealbumin; D006710:Homocysteine; D013481:Superoxides; D002097:C-Reactive Protein; C007957:homocysteine thiolactone; D019255:NADPH Oxidases