The mTOR signaling pathway in cardiac aging

Area of Science:

• Biogerontology
• Cardiovascular Biology
• Molecular Signaling

Background:

• The mammalian target of rapamycin (mTOR) pathway is central to nutrient sensing, cell growth, metabolism, and aging.
• mTOR complex 1 (mTORC1) critically regulates protein synthesis, autophagy, mitochondrial function, and metabolic health, influencing lifespan and healthspan.
• mTOR signaling is vital for cardiac development, homeostasis, and function, with hyperactivation linked to age-related cardiac dysfunction.

Purpose of the Study:

• To review the role of the mTORC1 pathway in organismal and cardiac aging.
• To highlight recent advances in understanding mTORC1's impact on aging, focusing on model organisms.
• To discuss downstream effectors and potential interactions with mTORC2 in cardiac aging.

Main Methods:

• Review of existing literature on model organisms (Drosophila and mice) of cardiac aging.
• Focus on downstream signaling pathways: S6 kinase and 4EBP1 (protein synthesis), ULK1 (autophagy).
• Discussion of the interplay between mTORC1, mTORC2, and cardiac aging.

Main Results:

• Hyperactivation of mTORC1 is associated with aging and age-related cardiac pathologies.
• Suppression of mTORC1, via calorie restriction or rapamycin, extends lifespan and improves cardiac function.
• mTORC1 regulates key aging processes including protein synthesis and autophagy in the heart.

Conclusions:

• The mTORC1 pathway is a key regulator of both organismal and cardiac aging.
• Targeting mTORC1 offers a promising strategy for mitigating age-related cardiac dysfunction and extending healthspan.
• Further research into mTORC1/mTORC2 interactions is crucial for understanding cardiac aging comprehensively.