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Updated: Aug 13, 2026

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06:18

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Established and emerging roles of lysosomal dysfunction in cardiac aging

Yohan Santin1,2,3, Ilias Simon4, Angelo Parini4,5

  • 1Unit of Inherited Cardiomyopathies, Centro Cardiologico Monzino IRCCS, Milan, Italy. yohan.santin@inserm.fr.

Nature Cardiovascular Research
|August 10, 2026
PubMed

Insights

Lysosomes are crucial for heart health during aging. Their dysfunction contributes to cardiovascular diseases, but restoring lysosomal function may preserve heart resilience.

Area of Science:

  • Cardiology
  • Cell Biology
  • Gerontology

Background:

  • Cardiac aging is a primary driver of cardiovascular diseases.
  • Lysosomes, once viewed as degradative organelles, are now known as vital metabolic and signaling hubs.
  • Lysosomal dysfunction significantly impacts the aging heart's health and function.

Purpose of the Study:

  • To review lysosome-dependent mechanisms in cardiac aging.
  • To highlight lysosomes as potential upstream drivers of cardiac aging.
  • To discuss therapeutic strategies for restoring lysosomal function in aging hearts.

Main Methods:

  • Literature review of established and emerging lysosome-dependent mechanisms.
  • Analysis of lysosomal roles across the hallmarks of cardiac aging.
  • Synthesis of knowledge gaps and therapeutic approaches.

Main Results:

  • Lysosomal dysfunction is implicated in various aspects of cardiac aging beyond impaired autophagy.
  • Lysosomes regulate critical functions including nutrient sensing, ion and lipid homeostasis, and inter-organelle communication.
  • Evidence from lysosomal storage disorders demonstrates their critical role in preventing early cardiomyopathy.

Conclusions:

  • Lysosomes are central and actionable targets for maintaining cardiac resilience during aging.
  • Therapeutic strategies aimed at restoring lysosomal function hold promise for combating age-related cardiovascular decline.
  • Further research is needed to fully elucidate lysosome-dependent mechanisms in cardiac aging and develop effective interventions.

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