Cytokine responses in young and old rhesus monkeys: effect of caloric restriction.
Caloric restriction (CR) is the only known intervention demonstrated to retard a great variety of aging processes, extend median and maximum life-span, and decrease the incidence of age-associated diseases in mammals. Paralleling findings from rodent studies, studies in rhesus monkeys (Macaca mulatta) suggest that CR may retard many age-sensitive parameters in primates. A recent study in rhesus monkeys showed age-related dysregulation of cytokine levels. Specifically, age-related increases in interleukin-10 (IL-10) and IL-6 proteins were observed in supernatants from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs), and interferon-gamma (IFN-gamma) protein exhibited an age-related decrease in phytohemagglutinin (PHA)-stimulated PBMCs. To investigate effects of CR on age-related changes in cytokine production, we obtained PBMCs from control and CR rhesus monkeys aged 6-7 and 22-25 years. We evaluated IL-10 and IL-6 protein and gene expression after exposure to LPS and IFN-gamma protein and gene expression after PHA stimulation. The results revealed significantly higher levels of IFN-gamma protein and gene expression in aged monkeys on CR for 2 years compared with controls. No significant CR effects were observed on IL-10 and IL-6 protein levels. IFN-gamma plays an important role in the initial defense mechanism against viral and microbial disease and cancer. Altered regulation of IFN-gamma in old CR rhesus monkeys may be a key factor in reducing cancer incidence and other age-associated diseases.
Mascarucci
Paolo
P
Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Taub
Dennis
D
Saccani
Simona
S
Paloma
Marjorie A
MA
Dawson
Harry
H
Roth
George S
GS
Lane
Mark A
MA
Ingram
Donald K
DK
D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D031204:Caloric Restriction; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008253:Macaca mulatta / Q000235:genetics / Q000276:immunology*; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D012313:RNA / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D016753:Interleukin-10; D012313:RNA; D007371:Interferon-gamma