# Mechanisms of dysregulated immunity with aging > **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $249,600 ## Abstract PROJECT SUMMARY/ABSTRACT Since our competitive renewal was funded last year, a global pandemic of a novel coronavirus has emerged that has resulted in higher number of deaths than prior coronavirus outbreaks (e.g., SARS, MERS). In particular, older patients (i.e., > 60 years old) exhibit markedly increased mortality from COVID-19 (SARS-CoV 2) infections. Hence, we urgently need to understand why older people exhibit worse outcomes during COVID- 19 infection. Based upon our preliminary data in mice employed in the parent R01, we hypothesize that during COVID-19 infection with aging, senescent alveolar epithelial cells (AEC) secrete neutrophil-attracting chemokines to induce neutrophil recruitment into the lung as well as PGE2, a pleiotropic lipid mediator, which suppresses alveolar macrophage proliferation and function. As alveolar macrophages are key in clearing debris and resolving inflammation, we postulate that impairments in alveolar macrophages with aging inhibit inflammation resolution during influenza infection. In Aim 1, we will leverage the human AEC culture described in the parent R01, to understand how aging impacts the inflammatory response to SARS-CoV2 infection in AEC and how this impacts neutrophil and alveolar macrophage. In Aim 2, we will leverage, through our collaborators, ongoing screens of repurposed FDA agents and novel anti-microbial peptides to identify novel therapeutics to mitigate the effects of SARS-CoV2 infection in AECs with aging. This administrative supplement is a natural extension of our funded NIA project on aging and the innate immune response to influenza, and could provide urgently needed insights to the mechanisms by which aging promotes mortality to COVID-19 and potential therapeutics to reduce the suffering and death of older people with COVID 19. ## Key facts - **NIH application ID:** 10135345 - **Project number:** 3R01AG028082-12S1 - **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR - **Principal Investigator:** Jane C Deng - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $249,600 - **Award type:** 3 - **Project period:** 2007-07-15 → 2024-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10135345 ## Citation > US National Institutes of Health, RePORTER application 10135345, Mechanisms of dysregulated immunity with aging (3R01AG028082-12S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10135345. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*