Skip to main content
Menu
Appearance

Pan-organ Immunosenescence Atlas

A story about how cells change over time

Created by Fan Lab at Yale University and the Cyberinfrastructure for Network Science Center at Indiana University

What is immunosenescence?

The immune system is a complex network of cells, tissues, organs, and the substances they make. It helps the body fight infections and other diseases. As we age, our immune system function becomes impaired. Our bodies have a harder time fighting off infections, controlling malignancies, and maintaining immune tolerance. This age-related deficiency in immune system function is called immunosenescence.

Illustrations of immune cells with a variety of shapes and internal structures

A key contributor to the immune system’s deterioration is cell senescence. This occurs when stress or damage to the cell causes it to exit the cell cycle. In this state of cell cycle arrest, the cell stops dividing but remains metabolically active. The senescent cell secretes a combination of bioactive molecules known as SASP—the senescence-associated secretory phenotype.

Stress or damage changes a normal cell into a senescent cell that secretes molecules associated with inflammation
Image source: National Institute on Aging, National Institutes of Health (2021), “Does Cellular Senescence Hold Secrets for Healthier Aging?”

Cell senescence has some very important benefits for our health. It aids in embryo development, helps our bodies respond to injury, and works to keep cancer cells from replicating.

However, as we age, senescent cells accumulate. This may contribute to “inflammaging,” a chronic, low-grade inflammation that can damage healthy tissue, promote disease progression, and accelerate the aging process. In many cases, the body relies on immune cells to clear senescent cells and prevent them from accumulating.

This function is impaired when immune cells themselves become senescent. Immune-cell senescence can also weaken the immune system’s ability to detect disease and migrate to sites of infection or injury. A better understanding of cellular senescence is crucial to developing treatments that could improve our quality of life as we age.

Comparison of a normal cell and a senescent cell, whose changes include cell-cycle arrest, secretions, enlarged shape, organelle dysfunction, and molecular damage
Image source: Figure 1 from “The Role of Cellular Senescence in Cardiovascular Disease” by Xu and colleagues (2025), reformatted under CC BY 4.0.

Researchers in the field of senescence biology work to identify the many varieties of senescent cells, locate where they reside in the body, and understand the effects they have on their surrounding environments. A cell’s senescence phenotype—the physical and biochemical traits the cell exhibits once it becomes senescent—can vary widely depending on the cell type and the tissue microenvironment. These diverse and context-specific phenotypes make research on immune cell senescence a particular challenge.

For starters, the immune system is distributed throughout the body. It consists of many organs and multiple tissue types with their own distinct structures and functions. Immune cell researchers often find that existing datasets (whether bulk or single-cell sequenced) underrepresent immune cells or lack them entirely. When immune cells are present, they typically lack robust data on senescence. The immune system is not contained in a single “immune organ.”

Likewise, there is no single “immune cell” with one particular function.

Examples of immune-related cell types: basophil, natural killer cell, B cell, plasma cell, T cell, neutrophil, dendritic cell, mast cell, eosinophil, endothelial cell, macrophage, and fibroblast

Instead, there are many cell types with different structures and roles. Different immune cell types exhibit different senescence patterns/features. Senescence can be difficult to detect in immune cells since some of the recognized markers of senescence are part of the normal functioning of many immune cells. Since context matters in the study of immune-cell senescence, research needs to analyze many tissue types across various anatomical structures.

To study how senescent cells behave in a living organism, scientists often conduct their research using samples from laboratory mice.

Mice have long been prized by medical researchers due to the many biological and genetic features they share with humans.

They are valuable to senescence research because their short lifespans allow scientists to observe the mechanics of aging over the space of months rather than decades.

This 3D mouse model shows the thymus, liver, spleen, and pancreas.

Front view of a translucent 3D mouse anatomical model with internal organs visible

The Cellular Senescence Network (SenNet) Program is one such effort that seeks to identify and characterize the differences in senescent cells across the body, across various states of human health, and across the lifespan. They are creating atlases of senescent cells, the differences among them, and the molecules they secrete, using data collected from multiple human and model organism tissues.

SenNet is teaming with the Human Reference Atlas (HRA) to study the possibility that senescent cells may alter their tissue microenvironments.

What changes can we see between young, aged, and treated tissue?

Researchers collected tissue from young mice, aged mice, and aged mice treated with dasatinib and quercetin (D&Q) drugs that target senescent cells.

In this comparison, young mice were 2 months old. Aged mice were 24 months old, including those treated with D&Q.

By mapping individual cells within liver, spleen, and thymus samples, researchers can compare how cellular patterns change with age—and whether those patterns change after treatment.

Each color represents a cell population. Compare where those populations appear, how densely they cluster, and which populations share the same neighborhoods across the three conditions.

Liver

  1. Young

    Cell population map of liver tissue from a young mouse, showing a rounded section divided by a large white channel

  2. Aged

    Cell population map of liver tissue from an aged mouse, showing a rounded section dominated by peach and brown regions

  3. Aged + D&Q

    Cell population map of D and Q-treated liver tissue from an aged mouse, showing peach and pale blue regions around an open center

Spleen

  1. Young

    Cell population map of spleen tissue from a young mouse, showing light blue clusters and a dark blue and pink region

  2. Aged

    Cell population map of spleen tissue from an aged mouse, showing multiple blue clusters surrounded by pink regions

  3. Aged + D&Q

    Cell population map of D and Q-treated spleen tissue from an aged mouse, showing blue clusters with green centers among pale pink regions

Thymus

  1. Young

    Cell population map of thymus tissue from a young mouse, showing broad pale blue, green, yellow, and orange regions

  2. Aged

    Cell population map of thymus tissue from an aged mouse, showing a narrow curved section with turquoise, dark blue, brown, and pink regions

  3. Aged + D&Q

    Cell population map of D and Q-treated thymus tissue from an aged mouse, showing a broad yellow and peach center bordered by turquoise and pink

What can we see?

Across the liver, spleen, and thymus, the colored cell populations differ in their distribution, clustering, and neighboring populations. These patterns also vary by organ, which is why each condition is compared within the same tissue.

What software exists to visualize cell differences over time?

The HRA Cell Distance Explorer tool can be used to measure how close cells are to one another, compare cell distances over time, and analyze cell neighborhoods in spatially resolved omics data.

The neighborhood-level analysis produced by the Cell Distance Explorer can be combined with more macro-level efforts to quantify spatial distribution to establish a metric and baseline that enable comparison across organs with different morphology.

  1. Let’s get familiar with the Cell Distance Explorer app.
  2. Show/hide cell types in the visualization and plots. Hide cell links from this table view. Update colors for individual cell types. Download CSVs for the current configurations of cell types, cell links, and cell type color map formatting.
  3. Use the node distance visualization to navigate cells spatially:
    • Zoom in and out with the mouse pinwheel or pinch using the trackpad
    • Pan using CTRL/CMD + mouse drag, right click + mouse drag, or use the keyboard arrows
    • Rotate the visualization using CTRL/CMD + keyboard arrows or with a mouse drag
  4. The violin plot shows cell-to-nearest-anchor cell distance distributions categorized by each cell type in the dataset.
  5. The histogram plot shows the cell-to-nearest-anchor cell distance distributions categorized by each cell type in the dataset.

Measuring distances between cells reveals how their spatial relationships change over time.

Let’s compare spleen samples representing a mouse at ages 2 months and 24 months. Using the Cell Distance Explorer, we measured how far each cell type is from its nearest endothelial cell—the anchor cell for this comparison.

The node-distance visualization maps each cell coordinate and its connection to the nearest anchor cell. Compare the 2-month and 24-month spleen samples to see how cell clusters, distances, and neighborhoods differ with age.

Young mouse, 2 months old
Young mouse spleen cell network showing cells and their links to the nearest endothelial cells
Aged mouse, 24 months old
Aged mouse spleen cell network showing cells and their links to the nearest endothelial cells

Cell types

  • Activated leukocyte
  • B cell
  • Dendritic cell
  • Endothelial
  • Erythroid
  • Granulocyte
  • Helper T cell
  • Macrophage
  • Naive B cell
  • Other
  • Plasma B cell
  • Stromal
  • T cell

Violin plots show how distances from endothelial cells are distributed for each cell type. Compare where each distribution sits, how widely it spreads, and whether its overall pattern differs between the two ages.

Young mouse, 2 months old
Violin plot of cell-to-endothelial-cell distances by cell type in the young mouse spleen sample
Aged mouse, 24 months old
Violin plot of cell-to-endothelial-cell distances by cell type in the aged mouse spleen sample

Histograms show how many cells occur at each distance from the nearest endothelial cell. The black line represents all cells, while the colored lines represent individual cell types. Compare where the lines peak, how quickly they rise or fall, and how far they extend across the two ages.

Cell types

  • Activated leukocyte
  • All cells
  • B cell
  • Dendritic cell
  • Erythroid
  • Granulocyte
  • Helper T cell
  • Macrophage
  • Naive B cell
  • Other
  • Plasma B cell
  • Stromal
  • T cell
Young mouse, 2 months old
Histogram of cell counts by distance from the nearest endothelial cell in the young mouse spleen sample
Aged mouse, 24 months old
Histogram of cell counts by distance from the nearest endothelial cell in the aged mouse spleen sample

The Cell Distance Explorer’s node-distance visualizations show the spatial grouping of cell types. The violin graphs summarize the shape and spread of each cell type’s distance distribution. The histograms show how many cells occur across those distances. This app makes cellular organization easier to identify while providing a starting point for closer analysis.

There is strong external evidence that immune senescence is implicated in tissue reorganization. Thus, monitoring the effects of senescence on the surrounding tissue, evaluating them, and treating them could vastly improve our health.