Lessons about inflammation and the biology of aging from Japan

Christopher Coe, Ph.D.


W.B. Cannon Professor, University of Wisconsin-Madison



Background.  It is commonly accepted that inflammatory activity increases in American and European adults as they age. However, this conclusion may not generalize to Japanese adults, who also have a lower age-related risk for cardiovascular disease and Type 2 diabetes.


Method.  Biomarkers were compared in 382 Japanese adults living in Tokyo (aged 30-79 years) from the Midlife in Japan study (MIDJA) with 1644 adults (25-84 years) from the Midlife in the United States project (MIDUS). Initially, the focus was on two commonly employed indicators of inflammatory activity, C-reactive protein (CRP) and interleukin-6 (IL-6), as well as markers of glucoregulation (glycosylated hemoglobin, HA1c) and lipid metabolism (Total Cholesterol/High Density Lipoprotein, Total/HDL).  Subsequently, a multiplex panel comprised of 4 cytokines was also compared: interleukin-6, interleukin-8, interleukin-10, and Tumor Necrosis Factor-alpha.


Result.  Both middle-aged and older Japanese adults have significantly lower levels of CRP and IL-6 than do American adults.  The CRP and IL-6 values for African-American adults were even higher than for white Americans of European family backgrounds.   Japanese adults also had lower HA1c values, although we found a 10% prevalence of Type 2 diabetes, which is still a concern and higher than in the past.  Diabetic individuals in both countries showed signs of elevated inflammatory activity.  Lipid profiles were particularly distinctive in Japan, with a much higher proportion of the beneficial high-density lipoprotein (HDL) as compared to Americans.  In contrast, elevated LDL levels are typically the primary clinical concern in overweight American adults when Total Cholesterol levels exceed 200 mg/dL (5.2 mmol/L).  Given the low IL-6 in Japanese adults, it was a surprise to discover that their levels of TNFalpha, IL-8 and IL-10 are in the same range as found for American adults.


Conclusion. Overall, Japanese adults are healthier than American adults and do not evince the typical indicators of ‘inflamm-aging’ commonly found to be elevated in older American and European populations. This difference likely reflects the benefits of the traditional Japanese diet and better weight control.  However, it was notable that when a Japanese adult attains a Body Mass Index (BMI) greater than 25, a level of adiposity considered to be acceptable for American adults, they do show an increased risk for elevated HA1c and type 2 diabetes.  Despite having much lower IL-6 and CRP levels (typically below 1 pg/mL and 1 mg/L, respectively), Japanese adults have IL-8, IL-10 and TNFalpha levels in the same range as middle-aged and older American adults.