| Title: | Evidence for an energy conservation model of inflammaging and immunosenescence in the US Health and Retirement Study and UK Biobank |
| Journal: | The Journals of Gerontology Series A |
| Published: | 7 May 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42096840/ |
| DOI: | https://doi.org/10.1093/gerona/glag119 |
Publication 20142
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Abstract
The development of chronic inflammation in later life (inflammaging), alongside changes in immune cell profiles and impaired pathogen defense (immunosenescence), contribute to health risk. However, these processes have been hypothesized as adaptive remodeling of the immune system in response to accumulating somatic damage. Here we consider a recently developed theoretical framework to understand their relationship: the Brain-Body Energy Conservation model of aging. This model views immunosenescence as part of an energy conserving response to the rising energy expenditure of inflammaging. This response promotes short term survival against somatic damage at the expense of future health risk. For example, naïve T cells, which enhance defense against future infections, decline with age, while proteins that suppress the immune response to infection, including IL-10, increase. GDF-15, which is produced in response to chronic inflammation and metabolic stress, and similarly suppresses the immune response to infection, also increases with age. We find evidence consistent with this model in the US Health and Retirement Study (HRS, n = 8,184) and UK Biobank (UKB, n = 40,510). Across both cohorts, the key inflammaging marker TNFR1 partially mediated the age-related increases in IL-10 and GDF-15. In the HRS flow cytometry data, TNFR1 also mediated age-related decreases in naïve T cells. Finally, we assessed vulnerability to a novel future infection using the UKB medical records data on hospitalization or death from COVID-19 (n = 586 hospitalized or died). TNFR1, IL-10, and GDF-15, measured pre-pandemic, all partially mediated the age-related increased risk.</p>
4 Authors
- Jacob E Aronoff
- Maximilien Franck
- Alan A Cohen
- Benjamin C Trumble
1 Application
| Application ID | Title |
|---|---|
| 772113 | Exploring inflammaging as a central mechanism driving age-related, system-wide functional decline and atrophy |
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