Infection, inflammation, height, and longevity

Abstract

Using historical data from cohorts born before the 20th century in four northern European countries, we show that increasing longevity and declining mortality in the elderly occurred among the same birth cohorts that experienced a reduction in mortality at younger ages. Concurrently, these cohorts also experienced increasing adult height. We hypothesize that both the decline in old-age mortality and the increase in height were promoted by the reduced burden of infections and inflammation. Thus, early growth and cardiovascular diseases of old age may share infectious and inflammatory causes rooted in the external environment.aging ͉ vascular disease ͉ mortality ͉ historical cohorts L ife expectancy has doubled during the last 250 years from preindustrial norms of 35-40 years (1, 2). Although all ages have benefited, the increases among the elderly began many decades after the increases at younger ages (3). We have hypothesized that the historical increase in life expectancy at the older ages was due in part to life-long reduction in exposure to chronic inflammation (4). It is well known that the survivors of birth cohorts with lowered early age mortality due to infections experienced lower mortality throughout adult life (5-8), a relationship we have characterized as the ''cohort morbidity phenotype'' (4). Others have proposed that mortality at young and old age is linked by improvements in nutrition and a reduction in organ damage due to infections (9,10). We add the reduction in lifelong exposure to inflammation to these explanations and develop in more detail the physiological mechanisms linking lifetime exposure to infections and late life health outcomes. We also consider inflammation as a possible link between childhood mortality and adult height (11).We argue that the demographic and economic revolutions beginning Ͼ200 years ago were accompanied by a physiological revolution, which occurred long before the benefits of modern medicine. The historical reduction in inflammation was an internal manifestation of the physiological revolution, which was also indexed by the historical increases in height. We propose a general model in which the reduction in lifelong levels of infections and inflammation reduced and delayed the atherosclerotic process and mortality due to heart disease and allowed increased height (Fig. 1). This heuristic model emphasizes the pathway from decreases in infection through reductions in inflammation but recognizes that other potential links include improvements in diet and nutrition and reductions in direct organ damage. Thus, our model considers a broader set of pathophysiological mechanisms linking health across the life course than presented heretofore.Extensive debate over the causes of the historical mortality decline has not resolved the relative roles of improved public health, vaccines, income, and nutrition (1, 12). However, all of these factors would have reduced exposure to, resistance to, or consequences of infections. The role we hypothesize for inflammation considers the ...

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