The redox state as a correlate of senescence and wasting and as a target for therapeutic intervention.
The loss of body cell mass (bcm) in senescence and wasting is poorly understood. We now show that the plasma cystine/acid soluble thiol ratio, ie, an indicator of the redox state, is increased in old age and cancer patients and correlated with a decrease in bcm and plasma albumin. A cause/effect relationship was suggested by two independent studies with N-acetyl-cysteine (NAC). NAC caused an increase in the bcm of healthy persons with high plasma cystine/thiol ratios, and treatment of cancer patients with NAC plus interleukin-2 caused an increase in bcm, plasma albumin, and functional capacity. Albumin levels below 680 micromol/L were associated with an increase in body water. Our studies suggest that the shift in the redox state may contribute to the loss of bcm and may provide a quantitative guideline for therapeutic intervention. Treatment of cancer patients with thiol-containing antioxidants may improve the quality of life.
Hack
V
V
Division of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Breitkreutz
R
R
Kinscherf
R
R
Röhrer
H
H
Bärtsch
P
P
Taut
F
F
Benner
A
A
Dröge
W
W
D000111:Acetylcysteine / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D016923:Cell Death; D002648:Child; D002675:Child, Preschool; D003553:Cystine / Q000097:blood; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010084:Oxidation-Reduction / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000097:blood
D016166:Free Radical Scavengers; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D003553:Cystine; D000111:Acetylcysteine