Related Experiment Video

Updated: Feb 14, 2026

Detection of Anti-MDA5 Autoantibodies Using HeLa Cells and Immunocytochemistry with Light Microscopy
10:55

Detection of Anti-MDA5 Autoantibodies Using HeLa Cells and Immunocytochemistry with Light Microscopy

Published on: October 31, 2025

882

Lack of MDA5 delays hematopoietic aging by modulating inflammaging and proteostasis in mice

Veronica Bergo1,2,3, Pavlos Bousounis4,5, Giang To Vu6

  • 1Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany. bergo95veronica@gmail.com.

Nature Communications
|February 12, 2026
PubMed

Insights

Melanoma differentiation-associated protein 5 (MDA5) reduction mitigates age-related hematopoietic stem cell (HSC) decline. Lower MDA5 levels preserve HSC function, metabolic fitness, and proteostasis, offering therapeutic potential for aging blood systems.

Area of Science:

  • Immunology
  • Aging Biology
  • Hematopoiesis

Background:

  • Chronic inflammation, termed "inflammaging," significantly impacts aging hematopoietic stem cells (HSCs) but remains poorly understood.
  • The role of innate immune sensors in HSC aging is an emerging area of research.

Purpose of the Study:

  • To investigate the role of the RNA sensor melanoma differentiation-associated protein 5 (MDA5) in hematopoietic stem cell (HSC) aging.
  • To elucidate the mechanisms by which MDA5 influences HSC function and age-related decline.

Main Methods:

  • Comparative analysis of aged wild-type and Mda5 knockout (Mda5-/-) mice.
  • Multiomic analyses including chromatin accessibility, transcriptomics, and metabolomics on HSCs.
  • Functional assays such as noncompetitive transplantation to assess HSC repopulation capacity.
  • Investigation of proteostasis regulators HSF1 and phospho-EIF2A.

Main Results:

  • Aged Mda5-/- mice showed reduced HSC accumulation and a myeloid-biased differentiation.
  • Mda5-/- HSCs exhibited enhanced quiescence and superior repopulation capacity compared to wild-type.
  • Mda5-/- HSCs displayed reduced inflammatory signaling, a youthful metabolic profile, and improved proteostasis.
  • Activation of HSF1 in aged wild-type HSCs partially restored youthful characteristics.

Conclusions:

  • MDA5 is a key factor in hematopoietic stem cell aging, driving inflammation and functional decline.
  • Attenuating MDA5-dependent inflammation preserves HSC function by maintaining metabolic fitness and proteostasis.
  • Targeting MDA5 offers a potential therapeutic strategy for mitigating age-related hematopoietic dysfunction.

More Related Videos

Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology14:57

Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology

Published on: March 23, 2011

95.3K
Minimizing Hypoxia in Hippocampal Slices from Adult and Aging Mice08:58

Minimizing Hypoxia in Hippocampal Slices from Adult and Aging Mice

Published on: July 2, 2020

8.5K

Related Concept Videos

Aging01:26

Aging

Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
833
The Effect of Aging on Tissues01:19

The Effect of Aging on Tissues

Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...
3.6K
Hypersensitivity Reactions: Delayed Hypersensitivity Reactions01:29

Hypersensitivity Reactions: Delayed Hypersensitivity Reactions

Delayed-Type Hypersensitivity (DTH), or Type IV hypersensitivity, is a cell-mediated immune response. It occurs when T cells, rather than antibodies, mediate a reaction to specific antigens. It is characterized by a delayed onset (1-2 days) and involves the recruitment of macrophages to the inflammation site.The initiation of a DTH response begins with the sensitization of T cells. During this phase, which lasts at least 1-2 weeks, antigen-specific T cells are activated, clonally expanded, and...
2
Multipotency of Hematopoietic Stem Cells01:19

Multipotency of Hematopoietic Stem Cells

The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
3.9K
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
4.1K
Role of Hematopoietic Growth Factors01:28

Role of Hematopoietic Growth Factors

Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
4.0K