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. 2023 Dec 19;120(51):e2317232120.
doi: 10.1073/pnas.2317232120. Epub 2023 Dec 8.

Three common assumptions about inflammation, aging, and health that are probably wrong

Thomas W McDade  1   2
Affiliations

Three common assumptions about inflammation, aging, and health that are probably wrong

Thomas W McDade. Proc Natl Acad Sci U S A. .

Abstract

Chronic inflammation contributes to the onset and progression of cardiovascular disease and other degenerative diseases of aging. But does it have to? This article considers the associations among inflammation, aging, and health through the lens of human population biology and suggests that chronic inflammation is not a normal nor inevitable component of aging. It is commonly assumed that conclusions drawn from research in affluent, industrialized countries can be applied globally; that aging processes leading to morbidity and mortality begin in middle age; and that inflammation is pathological. These foundational assumptions have shifted focus away from inflammation as a beneficial response to infection or injury and toward an understanding of inflammation as chronic, dysregulated, and dangerous. Findings from community-based studies around the world-many conducted in areas with relatively high burdens of infectious disease-challenge these assumptions by documenting substantial variation in levels of inflammation and patterns of association with disease. They also indicate that nutritional, microbial, and psychosocial environments in infancy and childhood play important roles in shaping inflammatory phenotypes and their contributions to diseases of aging. A comparative, developmental, and ecological approach has the potential to generate novel insights into the regulation of inflammation and how it relates to human health over the life course.

Keywords: aging; developmental origins; infectious disease; inflammation.

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Conflict of interest statement

Competing interests statement:The author declares no competing interest.

Figures

Fig. 1.
Fig. 1.
Contrasting perspectives on patterns of systemic inflammation: Hypothetical levels of CRP for three individuals over 8 wk according to the acute phase (Left) and chronic low-grade (Right) models. The acute phase model is characterized by low baseline CRP and high levels of within-individual variability over time. The chronic low-grade model is defined by low within-individual variability and stable between-individual differences in CRP.
Fig. 2.
Fig. 2.
CRP variability for adults in lowland Ecuador over four weekly sampling intervals. CRP concentrations are plotted for the subset of 18 individuals with CRP > 3 mg/L at any of the sampling intervals (34 participants had CRP < 3 mg/L across all intervals and are not plotted). There are no cases of chronic inflammation. The figure is adapted from data presented in ref. .
Fig. 3.
Fig. 3.
Life course model of the associations among early environments, inflammatory phenotypes in adulthood, and diseases of aging. During sensitive periods of immune development, nutritional, psychosocial, and microbial environments can bias inflammation toward a more tightly regulated, acutely responsive phenotype (Top, blue) that does not impact diseases of aging. Alternatively, early environments can lead to dysregulated and chronic inflammation in adulthood (Bottom, red), which contributes to the pathophysiology of age-related increases in morbidity and mortality.
See this image and copyright information in PMC

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    Langlois J. Langlois J. Proc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2321324121. doi: 10.1073/pnas.2321324121. Epub 2023 Dec 26. Proc Natl Acad Sci U S A. 2024. PMID: 38147557 Free PMC article. No abstract available.

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