Nature agingSep 30, 2025

Fragments from broken elastin trigger aging by activating the innate immune system

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Elastin-derived extracellular matrix fragments may promote aging by activating innate immune signaling through NEU1.

Evidence

This mixed human, mouse, immune-humanized mouse, and pig study linked circulating ECM fragments with age, tested lifespan effects of elastin fragments, and found NEU1 inhibition extended lifespan by up to 17% in naturally aged mice.

Caveat

The strongest intervention evidence is preclinical, and the human data show correlations with aging indicators rather than demonstrated lifespan benefit from NEU1 inhibition.

Simplified

The roles of cells in systemic aging have been systematically investigated, while the roles of the extracellular matrix (ECM) and its degradation have been largely overlooked. Herein, we show that the serum contents of elastin-, hyaluronic acid- and fibronectin-derived fragments are all positively correlated with age. Elastin-derived fragments exhibited the most potent lifespan-shortening effects in mice and a positive correlation with various aging indicators in a human cohort (n = 1,068). Mechanistically, the VGVAPG oligopeptide (E-motif) in elastin-derived fragments activated monocytes and macrophages through NEU1, a component of the elastin receptor complex, which consequently caused an inflammatory response. Therapeutically, a NEU1 inhibitor extended lifespan by up to 17% in wild-type naturally aged mice and alleviated aging-related phenotypes in wild-type mice, immune-humanized mice and pigs. This study uncovers that degraded ECM acts as a circulating driver of aging, providing an anti-aging intervention strategy focused on particular elastin fragment signals.

Key numbers

1,068

Cohort Size

Number of human participants studied for correlations with elastin fragment levels.

17%

Lifespan Extension

Percentage increase in lifespan observed in mice treated with the inhibitor DANA.

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Funding

Competing interests

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Fragments from broken elastin trigger aging by activating the innate immune system

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Abstract

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