| Title: | Exploring inflammaging as a central mechanism driving age-related, system-wide functional decline and atrophy |
| Lead Institution: | Arizona State University |
| Principal investigator: |
Application 772113
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About
Later life is characterized by functional decline and atrophy across biological systems. This includes tissue atrophy in the muscles, fat depots, bones, the brain, and immune tissue. Functional decline in various hormonal systems is also observed, including sex and growth hormones. However, at the same time, there is an up-regulation of inflammatory signaling, termed "inflammaging". A recently proposed theoretical model suggests that inflammaging is the central regulator of these system-wide changes. Specifically, damaged and dysfunctional cells accumulate with age, which become hyper-metabolic and pro-inflammatory. In order to offset the increasing energy expenditure of these cells throughout the body, the brain orchestrates "energy-saving" mechanisms, divesting energy from any function not immediately necessary for survival. This includes sex and growth hormone signaling, muscle and fat mass, bone density, certain immune tissues like the thymus, and eventually brain tissue. I propose to test this model using the UK BioBank. Specifically, I propose to use proteomic data to assess whether markers of inflammaging (e.g., IL-6, TNF, GDF15) mediate the relationship between advancing age and disease states (proxies for accumulating damaged/dysfunctional cells) and the suite of system-wide decline and atrophy. This includes body scans of muscle and fat mass, bone density, and brain volume. I also plan to assess hormonal declines, including sex hormone-binding globulin (SHBG), total testosterone (TT), bioavailable testosterone (BT), estradiol (E2), growth hormone (GH), and insulin-like growth hormone (IGF)-1. Finally, I plan to assess declines in immune tissue, assessed using lymphocyte counts.1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 20142 | Evidence for an energy conservation model of inflammaging and immunosenescence in the US Health and Retirement Study and UK Biobank | Jacob E Aronoff (+3) | 2026 | The Journals of Gerontology Series A |
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