# Immunobiology and alveolar physiology of the aging lung

> **NIH NIH U01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $643,703

## Abstract

Project Summary
The elderly population is expected to double in the next 40 years, and therefore aging-related diseases are
likely to become a major healthcare burden. Lung diseases, including emphysema, chronic obstructive
pulmonary disease, and interstitial lung disease, and general lung pathologies including acute lung injury (ALI)
and the associated acute respiratory distress syndrome (ARDS), increase dramatically in the elderly, although
the underlying causes and mechanisms remain undefined. Importantly, aging is associated with a number of
changes in lung physiology and lung immunity, including a decreased vital capacity, decreased mucociliary
clearance, and increased susceptibility to both bacterial and viral infections. Changes in lung physiology and
pathogen susceptibility may be related; however, there is little known regarding the impact of these age-related
physiologic changes on surveillance of the lung by the immune system. Identifying molecular changes in these
processes with age can lead to new therapeutic interventions to help protect the aging lung and reduce
disease incidence. We have established a novel human tissue resource where we obtain multiple lymphoid
and mucosal tissues from organ donor of all ages, including all ages of adulthood up to the 9th decade of life.
Importantly, we obtain lungs, lung-associated and peripheral lymphoid tissues, enabling novel study of aging-
associated changes over a continuum of decades. Our central hypothesis is that with age, there is decreased
immune surveillance and protection both from lung-resident immune cells and lung-associated lymph nodes,
resulting in decreased lung cell integrity and increased susceptibility to damage. In the proposed study, we will
take a multi-disciplinary approach to study the interaction between the lung immune system and lung
epithelium as a function of age. In aim 1 we will identify how lung resident immune cells and lung-associated
lymph nodes (LN) alter with age. We will use high dimensional cellular and molecular profiling using high
parameter flow cytometry and whole transcriptome profiling to assess changes in immune cell populations, and
immunofluorescence imaging to determine the frequency and localization of lung-resident immune cells, and
the functional activity of LN through examination of LN follicles. In aim 2, we will use real time optical imaging
of the human lung to determine the effect of age on the quality of the alveolar-capillary fluid barrier,
mitochondrial function in the alveolar epithelium, and the extent to which resident AMs maintain gap junctional
and paracrine communication with the alveolar epithelium. In aim 3, we will define the age-drive gene
expression program in all lung cells, using single cell RNA-Seq to assess how gene expression programs that
define lung epithelial cells, endothelial cells, innate and adaptive immune cells will be altered and the kinetics
of these alterations. The proposed studies will reveal new insight...

## Key facts

- **NIH application ID:** 9842008
- **Project number:** 5U01HL145547-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jahar Bhattacharya
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $643,703
- **Award type:** 5
- **Project period:** 2019-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842008

## Citation

> US National Institutes of Health, RePORTER application 9842008, Immunobiology and alveolar physiology of the aging lung (5U01HL145547-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9842008. Licensed CC0.

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