ArticleProceedings of the National Academy of Sciences of the United States of America2018
Thymic involution and rising disease incidence with age.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 217 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
217 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Rethinking immune studies: population-level immune variations and the path forward.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Pooled it
- Mesenchymal thymic niche cells enable regeneration of the adult thymus and T cell immunity.Nature biotechnology · 2026Article
- Thymic function as a central determinant of immune competence and clinical outcomes.Seminars in immunopathology · 2026Review
- Long-Term Cancer and Mortality After Thymectomy.European journal of neurology · 2026Article
- Analysis of Human Thymopoiesis Reveals Rapid Postnatal Remodeling of Thymocytes Within the First 3 Months of Life.European journal of immunology · 2026Article
- Clinical rationale for thymic restoration in adult immunosenescence.Immunity & ageing : I & A · 2026Review
- What Do We Know About Immune System Aging from Human and Animal Studies?International journal of molecular sciences · 2026Review
- Foxp1 controls Fezf2-dependent gene expression, mimetic mTEC diversity, and thymic central tolerance.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Aging diminishes thymic output, reduces naive T cells, promotes memory T-cell accumulation, and impairs thymic regeneration.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Article
- From Development to Aging: Dynamic Roles of the Thymic Medulla in T Cell Biology.Immunological reviews · 2026Review
- Morphometric analysis of the thymic epithelial cell network using integrated and orthogonal digital pathology approaches.Communications biology · 2026Article
- CT-Based Thymic Morphology as an Imaging Surrogate of Immune Ageing and Its Association with Coronary Artery Calcification-A Hypothesis-Generating Observational Study.Biomedicines · 2026Article
- Thymic health consequences in adults.Nature · 2026Article
- Article
- Association between immune cells and multiple cancers: Insights from Mendelian randomization and gene-based analysis.iScience · 2026Article
- Age-related thymic involution: Mechanistic insights and rejuvenating approaches to restore immune function.Science advances · 2026Review
- The neutrophil-to-lymphocyte ratio as a marker of immunosenescence and COVID-19 outcomes in the elderly: A narrative review.Physiological reports · 2026Review
- Mechanical Insights into the Distinct Effects of Ovariectomy Versus Adrenalectomy on Age-Related Thymic Atrophy in Female Mice.International journal of molecular sciences · 2026Article
- Is Thymic Involution Truly a Deterioration or an Adaptation?Bulletin of mathematical biology · 2026Article
- Of Barriers and Loops-How Evolution Limits Most Cancer Risks to Older Ages.Cancer discovery · 2026Review
157 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.