ECM: The Overlooked Foundation – A New Role in Aging

Over the past decade, the Hallmarks of Aging framework has become central to understanding how the body ages. Originally proposed by López-Otín and colleagues in 2013, it identified nine key biological processes. In 2023, the model was expanded to twelve, adding chronic inflammation (inflammaging) and gut microbiome imbalance (dysbiosis) as new contributors to aging.

However, studies in recent years have shown that the extracellular matrix (ECM)—the structural network that supports and regulates cell function—plays a crucial role in the aging process. As a result, it has increasingly been recognized as a potential addition to the Hallmarks of Aging.

What is the ECM?

The extracellular matrix (ECM) is a complex network of proteins and molecules located outside of cells. It provides structural support and plays a key role in cell signaling, influencing cell growth, division, and death. Major components of the ECM include collagen, elastin, glycoproteins, and proteoglycans—all of which help maintain the strength and elasticity of tissues.

 

How ECM Changes Affect Aging

As we get older, the extracellular matrix (ECM) changes in ways that speed up aging and affect how our tissues work:

• Build-up of Cross-links: With age, cross-links form between ECM proteins, such as glucosepane—an advanced glycation end product. This leads to stiffening and loss of elasticity in the ECM, disrupting cell-to-cell communication and impairing tissue coordination.
• Changes in ECM Composition: The levels of certain proteins, such as collagen, decline, while others may increase. These imbalances alter the structure and function of the ECM, compromising tissue integrity.
• Chronic Inflammation: ECM changes can trigger persistent low-grade inflammation, a key driver of aging known as inflammaging.

 

ECM: A New Hallmark of Aging

The extracellular matrix (ECM) was not originally included among the 12 Hallmarks of Aging proposed by López-Otín et al. (2013). However, recent studies published in Cell and Nature Reviews Molecular Cell Biology in 2023 have identified “ECM dysregulation” as a promising candidate hallmark.

This is because ECM changes affect multiple body systems, accumulate with age, contribute to disease development, and—if properly managed—could slow down the overall aging process.

 

ECM and the Hallmarks of Aging

• Changes in the extracellular matrix (ECM) are closely linked to several key factors within the Hallmarks of Aging, including:
• Stem Cell Exhaustion: Damaged ECM reduces stem cells’ ability to repair and renew tissues.
• Altered Cell Communication: Changes in the ECM disrupt how cells send and receive signals, which affects aging.
• Chronic Inflammation: A worn-out ECM can cause ongoing inflammation, which speeds up aging.

Guidelines to Protect and Maintain ECM Health

• Control Blood Sugar Levels: Consuming too much sugar can lead to glycation, a process where sugar binds to ECM proteins, causing harmful cross-links that stiffen the ECM.
• Consume Antioxidants: Antioxidants like vitamin C, vitamin E, and coenzyme Q10 help reduce damage to the ECM caused by oxidative stress.
• Exercise Regularly: Physical activity stimulates the production of collagen and elastin in the ECM and helps reduce chronic inflammation.
• Avoid Excessive UV Exposure: UV rays can damage ECM proteins and trigger enzymes that break down the ECM.
• Eat Nutrient-Rich Foods: Foods rich in essential amino acids, vitamin C, zinc, and copper support the synthesis of collagen and elastin in the ECM.

 

Research References

• Dorronsoro et al., 2023 — “Extracellular matrix regulation of aging and disease: A new hallmark?”

           This study proposes that ECM dysregulation meets the criteria to be considered a new hallmark of aging.

• López-Otín et al., 2013 — “The Hallmarks of Aging,” Cell

 The foundational article that introduced the original nine hallmarks of aging.

López-Otín et al., 2023 — “Hallmarks of Aging: An expanding universe,” Cell
 This updated review expands the hallmarks from nine to twelve and highlights ECM dysregulation as a “candidate hallmark.”

Henke et al., 2020 — “ECM microenvironment and aging: A systems biology perspective,” Nature Reviews Molecular Cell Biology
 Analyzes the impact of ECM on cellular function and tissue repair.

Frantz et al., 2010 — “The extracellular matrix at a glance,” Journal of Cell Science
 Provides an overview of ECM structure and its roles in the body.