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...
| Main Authors: | , , , |
|---|---|
| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
National Academy of Sciences
2018
|
| _version_ | 1826283210730897408 |
|---|---|
| author | Palmer, S Albergante, L Blackburn, CC Newman, TJ |
| author_facet | Palmer, S Albergante, L Blackburn, CC Newman, TJ |
| author_sort | Palmer, S |
| collection | OXFORD |
| description | 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 law model 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. |
| first_indexed | 2024-03-07T00:55:29Z |
| format | Journal article |
| id | oxford-uuid:87f06a2c-986a-47f6-a8ea-3aedb8c52ae9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:55:29Z |
| publishDate | 2018 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:87f06a2c-986a-47f6-a8ea-3aedb8c52ae92022-03-26T22:13:45ZThymic involution and rising disease incidence with age.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:87f06a2c-986a-47f6-a8ea-3aedb8c52ae9EnglishSymplectic ElementsNational Academy of Sciences 2018Palmer, SAlbergante, LBlackburn, CCNewman, TJFor 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 law model 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. |
| spellingShingle | Palmer, S Albergante, L Blackburn, CC Newman, TJ Thymic involution and rising disease incidence with age. |
| title | Thymic involution and rising disease incidence with age. |
| title_full | Thymic involution and rising disease incidence with age. |
| title_fullStr | Thymic involution and rising disease incidence with age. |
| title_full_unstemmed | Thymic involution and rising disease incidence with age. |
| title_short | Thymic involution and rising disease incidence with age. |
| title_sort | thymic involution and rising disease incidence with age |
| work_keys_str_mv | AT palmers thymicinvolutionandrisingdiseaseincidencewithage AT albergantel thymicinvolutionandrisingdiseaseincidencewithage AT blackburncc thymicinvolutionandrisingdiseaseincidencewithage AT newmantj thymicinvolutionandrisingdiseaseincidencewithage |