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Download Stress, Inflammation, and Aging - Nicolas Rohleder
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STRESS, INFLAMMATION, AND AGING Nicolas Rohleder Department of Psychology Brandeis University, STRESS, INFLAMMATION & AGING Stress Aging Inflammation 1 STRESS, INFLAMMATION & AGING Stress Aging Inflammation local systemic sepsis Chronic low-grade Inflammation STRESS, INFLAMMATION & AGING Chronic low-grade Inflammation DYSREGULATED NORMAL IL-6 CRP Cortisol IL-6 & CRP Infection time (hours to days) (YEARS) 2 STRESS, INFLAMMATION & AGING Chronic low-grade Inflammation DYSREGULATED NORMAL IL-6 CRP Cortisol IL-6 & CRP acute “healing“ Infection response time (hours to days) long-term over-activity (YEARS) lack of infectious stimulus gradual increase Low levels of inflammatory markers STRESS, INFLAMMATION & AGING Chronic low-grade Inflammation Effects of chronic low-grade inflammation • • triggers local inflammatory responses throughout the body • Stimulates atherosclerosis > MI & strokes (e.g. Danesh, 1999) • Stimulates insulin resistance / type 2 diabetes (Hotamisligil, 2006) • Elicits depressive symptoms, fatigue, and cognitive decline CRP and IL-6 predict mortality in older people (e.g. Ershler, 1993; Harris et al., 1999) Inflammation - the “silent killer” 3 STRESS, INFLAMMATION & AGING Chronic low-grade Inflammation Stress Aging Inflammation increases with age IL-6 & CRP 0 10 20 30 40 50 60 70 80 90 Age (years) STRESS, INFLAMMATION & AGING Chronic low-grade Inflammation Stress Aging IL-6 & CRP 0 10 20 30 40 50 60 70 80 90 Age (years) 4 STRESS, INFLAMMATION & AGING Intracellular Regulation of Inflammation LPS danger TLR-4 Iκ κB Degradation p50 Iκ Iκ κκ-B -B p65 p50 p65 Inflammatory mediators: Interleukin-6 (IL-6), IL-1beta, TNFalpha, ICAM-1, VCAM-1, etc. STRESS, INFLAMMATION & AGING Role of Stress Systems SNS NE LPS β -AR TLR-4 HPA axis NE GC Iκ κB Degradation p50 Iκ κ-B GR-α α GC p65 p50 GR-α α GC p65 pro-inflammatory Inflammatory gene products anti-inflammatory 5 STRESS, INFLAMMATION & AGING Chronic low-grade Inflammation Stress Aging behavior biology inactivity smoking diet adiposity norepinephrine cortisol IL-6 & CRP 0 10 20 30 40 50 60 70 80 90 Age (years) STRESS, INFLAMMATION & AGING Chronic low-grade Inflammation DYSREGULATED IL-6 & CRP Time (YEARS) is stimulated by: • age, health behaviors, overweight, smoking, infections, psychosocial factors leads to: • atherosclerosis, coronary heart disease, stroke, depression, fatigue, pain 6 STRESS, INFLAMMATION & AGING Chronic low-grade Inflammation Stress Aging Outlook & Open Questions • Is low-grade inflammation a natural consequence of aging? • Is low-grade inflammation the consequence of life-long stress exposure? STRESS, INFLAMMATION & AGING Stress of caregiving to a brain cancer patient Rohleder et al. (in press) J Clin Oncol 7 STRESS, INFLAMMATION & AGING Chronic low-grade Inflammation Stress Aging Outlook & Open Questions • Is low-grade inflammation a natural consequence of aging? • Is low-grade inflammation the consequence of life-long stress exposure? • What is the contribution of stress-induced changes in health behaviors? 8
