Why does aging make a person's immune organs filled with fat?

A new study by researchers at Uppsala University presents new findings explaining why human lymph nodes lose function with age, and the impact
on the effectiveness of our immune system.
This article has been published in The Journal of Pathology
.

Lymph nodes are usually the headquarters
of our immune system.
When we are infected or vaccinated, lymph nodes are where immune cells gather, activate, and proliferate to be able to mobilize effective immune defenses
.
However, as we age, the normal tissue in the lymph nodes (interstitium) is gradually replaced
by adipose tissue (fat).
This phenomenon is called lymphadenadociomatosis
.
While lipomatosis is common and increases with age, it has rarely been discussed and studied
by researchers before.

Through careful analysis of more than 200 lymph nodes, Maria Ulvmar's team demonstrated that lipomatosis begins in the central part of the lymph nodes, the medulla, and provided evidence
that lipomatosis is associated with the transformation of the node's supporting cells (fibroblasts) into fat cells.
They also showed that specific types of fibroblasts located in the medulla are more likely to turn into fat cells
.

Studies have shown that even in the early stages of lipomatosis, negative changes
occur that impair the lymph nodes to provide effective immunity.
In other observations, they noted that specialized blood vessels and lymphatic vessels that normally provide channels for immune cells to and from the lymph nodes were destroyed in the part of the lymph nodes that formed fat
.
Therefore, even in the early stages, lymphadenopathy can be an important factor
in the poorer response to vaccination in older people.
Eventually, fat completely controls the lymph nodes, rendering them dysfunctional
.

Tove Bekkhus, lead author of the study, said: "Our study is the first step in understanding why liposis occurs and the first step
towards finding long-term goals to prevent its progression and lymph node destruction.
"

The researchers have not been able to mimic the effects they observed in human lymph nodes in animal models, which are often used to study the effects of
aging.
This underscores the importance of
research based on direct analysis of aging-related changes in human subjects.

"I hope our work will inspire interest from other researchers to include lymphadenal lipomatosis as a factor
when studying the response of older adults to vaccination and infection.
" The changes we observed are also highly relevant for cancer research, because in several types of cancer, lymph nodes are where cancer cells first spread," explains Maria H.
Ulvmar, a researcher at Uppsala University who led the study
.

"Our publication provides the first chapter
in a story about the loss of lymph node fat and function as we age.
We will now continue to develop this story by designing new research to learn more about the potential causes and consequences of these changes," Ulvmar said
.

The main material analyzed in the study included biological samples
from Uppsala Biobank.
These samples have been analyzed
using advanced image analysis.
The study also includes analysis and experiments using cell cultures from primary stromal cells, as well as bioinformatics analysis of gene expression (RNA level) from two single-cell RNA sequencing (RNAseq) datasets in mice and humans, previously published by others but now analyzed in this study, to find answers to new specific questions
.