Thymic involution and rising disease incidence with age

For many cancer types, incidence rises rapidly with age as an apparent power law, supporting the idea that cancer is caused by a gradual accumulation of genetic mutations. Similarly, the incidence of many infectious diseases strongly increases with age. Here, combining data from immunology and epide...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 115; no. 8; pp. 1883 - 1888
Main Authors Palmer, Sam, Albergante, Luca, Blackburn, Clare C., Newman, T. J.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 20.02.2018
Subjects
Accumulation
Age
Biological Sciences
Cancer
Epidemiology
Immune system
Immunology
Incidence
Infectious diseases
Lymphocytes
Lymphocytes T
Mathematical models
Mutation
Power law
Risk factors
Thymic involution
Thymus
driver mutations
thymus
cancer
infectious disease
T cell
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Summary:For many cancer types, incidence rises rapidly with age as an apparent power law, supporting the idea that cancer is caused by a gradual accumulation of genetic mutations. Similarly, the incidence of many infectious diseases strongly increases with age. Here, combining data from immunology and epidemiology, we show that many of these dramatic age-related increases in incidence can be modeled based on immune system decline, rather than mutation accumulation. In humans, the thymus atrophies from infancy, resulting in an exponential decline in T cell production with a half-life of ∼16 years, which we use as the basis for a minimal mathematical model of disease incidence. Our model outperforms the power lawmodel with the same number of fitting parameters in describing cancer incidence data across a wide spectrum of different cancers, and provides excellent fits to infectious disease data. This framework provides mechanistic insight into cancer emergence, suggesting that age-related decline in T cell output is a major risk factor.
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2Present address: Solaravus, Cupar KY15 5AS, United Kingdom.
Author contributions: S.P. and T.J.N. designed research; S.P., L.A., C.C.B., and T.J.N. performed research; S.P., L.A., and T.J.N. contributed new reagents/analytic tools; S.P., L.A., and T.J.N. analyzed data; and S.P., L.A., C.C.B., and T.J.N. wrote the paper.
Edited by Bruce S. McEwen, The Rockefeller University, New York, NY, and approved December 26, 2017 (received for review August 28, 2017)
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1714478115