Circulating elastin fragments drive systemic aging: Where do pro-aging elastin fragments come from? A mini-review.

Area of Science:

• Biogerontology
• Molecular Biology
• Tissue Engineering

Background:

• Circulating elastin fragments are implicated in inflammaging and systemic aging.
• Elastin, a key structural protein, is concentrated in mechanically stressed tissues like the aorta, lungs, and skin.
• Age-related tissue degeneration and increased elastolytic protease activity may cause elastin fragment release.

Purpose of the Study:

• To identify the primary anatomical sources of circulating elastin fragments during aging.
• To examine the elastolytic enzymes responsible for generating these fragments.
• To establish a framework for tissue-targeted interventions against the ECM-inflammaging axis.

Main Methods:

• Review of existing literature on elastin distribution, aging, and protease activity.
• Analysis of proposed mechanisms for elastin fragment generation in different tissues.
• Synthesis of information to delineate the relative contributions of various anatomical sources.

Main Results:

• Key anatomical compartments contributing elastin fragments include the aorta, lungs, and skin.
• Upregulated elastolytic proteases (neutrophil elastase, MMPs) are crucial in fragment generation.
• Chronic release of bioactive fragments fuels inflammaging and systemic aging.

Conclusions:

• Understanding the sources of circulating elastin fragments is critical for comprehending inflammaging.
• Targeting specific anatomical sources and their associated proteases offers a potential therapeutic strategy.
• This knowledge provides a mechanistic basis for developing interventions to disrupt the ECM-inflammaging axis.