# Reversing aging-induced lymphatic dysfunction to improve immune function

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $248,600

## Abstract

One significant problem with aging is a reduced ability to generate immune responses to bacterial, viral and
fungal infections, leading to more hospitalizations and putting elderly people at greater risk of death from common
infections. This problem has been starkly demonstrated by the greater rates of hospitalization and death from
SARS-CoV-2 infections in older people. Older people also have lower rates of generating immunity after
vaccination, leaving them vulnerable to common infectious diseases. Thus, there is a need to improve the
function of the immune system in elderly people in order to lower rates of infections and their associated
burdens. The lymphatic system—consisting of lymph nodes and lymphatic vessels—plays a central role in
generating immune responses, which depend on lymph flow to carry antigens from the pathogen to lymph nodes
to activate immune cells. We, and others, have shown that lymphatic function and lymph flow are reduced in
aged animals. The reduced lymph flow limits antigens from getting to lymph nodes and initiating an immune
response. Thus, poor lymphatic function can be one potential factor that contributes to reduced immune function
in the elderly. The mechanisms behind reduced lymphatic function in aged mice are not well characterized.
Further, there are no FDA approved drugs indicated to improve lymphatic function. The overall goal of the
proposed project is to define the mechanisms that drive the aging-related reduction in lymphatic
function in order to target these mechanisms to boost both lymphatic and immune function in aged mice.
Lymphatic muscle cells (LMCs) are a natural target cell to boost lymphatic function as they drive lymph flow by
causing rapid lymphatic vessel contractions. LMCs however have not been well characterized and are often
considered vascular smooth muscle cells, despite clear phenotypic differences in the behavior of these cell types.
Building on our recently generated transcriptome of LMCs, we will compare the transcriptomes of LMCs from
freshly isolated collecting lymphatic vessels from young and old mice in the proposed work. These data will
identify mechanistic pathways to target in order to boost lymphatic function in aged animals. Further, we will
determine whether the transcriptional changes are dictated by age-related microenvironmental differences. We
will also test the causal relationship between poor immune function and poor lymphatic function in aged mice by
increasing lymphatic pumping pharmacologically. Long-term, we will validate our findings in human tissue and
develop therapeutic approaches to boost lymphatic function in elderly people. This work will form the basis for
the first FDA approved drugs to improve lymphatic function. Our novel therapeutic concept would lead to fewer
hospitalizations and deaths due to infections in elderly people as well as better vaccine efficacy, which will
prevent common viruses, such as influenza or SARS-CoV-2, from driving mortality in e...

## Key facts

- **NIH application ID:** 10371505
- **Project number:** 1R21AG072205-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** TIMOTHY P PADERA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $248,600
- **Award type:** 1
- **Project period:** 2022-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371505

## Citation

> US National Institutes of Health, RePORTER application 10371505, Reversing aging-induced lymphatic dysfunction to improve immune function (1R21AG072205-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10371505. Licensed CC0.

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