Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty

• Published in: Annual review of medicine Vol. 51; no. 1; pp. 245 - 270
• Main Authors: Ershler, William B, Keller, Evan T
• Format: Journal Article
• Language: English
• Published: Palo Alto, CA 94303-0139 Annual Reviews 01.01.2000; 4139 El Camino Way, P.O. Box 10139; USA
• Subjects: Age Factors; Aged; Aging - genetics; Alzheimer Disease - etiology; Analytical, structural and metabolic biochemistry; Biological and medical sciences; cachexia; cytokines; dementia; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Glucocorticoids - pharmacology; Humans; immune dysregulation; immunodeficiency; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Lymphoproliferative Disorders - etiology; osteoporosis; Osteoporosis - etiology; Protein hormones. Growth factors. Cytokines; Proteins; Receptors, Interleukin-6 - physiology; sarcopenia; Human; Nervous system diseases; Alzheimer disease; Ageing; Cytokine; Diseases of the osteoarticular system; Activator gene; Malignant hemopathy; Bone disease; Inflammation; Gene expression; Cerebral disorder; Interleukin 6; Osteoporosis; Regulation(control); Lymphoproliferative syndrome; Central nervous system disease; Complication; Degenerative disease; Biological effect; Sex steroid hormone
• ISSN: 0066-4219; 1545-326X
• DOI: 10.1146/annurev.med.51.1.245

Interleukin-6 (IL-6) is a proinflammatory cytokine that is normally tightly regulated and expressed at low levels, except during infection, trauma, or other stress. Among several factors that down-regulate IL-6 gene expression are estrogen and testosterone. After menopause or andropause, IL-6 levels are elevated, even in the absence of infection, trauma, or stress. IL-6 is a potent mediator of inflammatory processes, and it has been proposed that the age-associated increase in IL-6 accounts for certain of the phenotypic changes of advanced age, particularly those that resemble chronic inflammatory disease [decreased lean body mass, osteopenia, low-grade anemia, decreased serum albumin and cholesterol, and increased inflammatory proteins such as C-reactive protein (CRP) and serum amyloid A]. Furthermore, the age-associated rise in IL-6 has been linked to lymphoproliferative disorders, multiple myeloma, osteoporosis, and Alzheimer's disease. This overview discusses the data relating IL-6 to age-associated diseases and to frailty. Like the syndrome of inappropriate antidiuretic hormone, it is possible that certain clinically important late-life changes are due to an inappropriate presence of IL-6.