#1

The removal of damaged mitochondrial components through a process called mitochondrial autophagy (mitophagy) is essential for the proper function of the mitochondrial network. Hence, mitophagy is vital for the health of all aerobic animals, including humans. Unfortunately, mitophagy declines with age. Many age-associated diseases, including Alzheimer’s and Parkinson’s, are characterized by the accumulation of damaged mitochondria and oxidative damage. Therefore, activating the mitophagy process with small molecules is an emerging strategy for treating multiple aging diseases. Recent studies have identified natural and synthetic compounds that promote mitophagy and lifespan. This article aims to summarize the existing knowledge about these substances. For readers’ convenience, the knowledge is presented in a table that indicates the chemical data of each substance and its effect on lifespan. The impact on healthspan and the molecular mechanism is reported if known. The article explores the potential of utilizing a combination of mitophagy-inducing drugs within a therapeutic framework and addresses the associated challenges of this strategy. Finally, we discuss the process that balances mitophagy, i.e. mitochondrial biogenesis. In this process, new mitochondrial components are generated to replace the ones cleared by mitophagy. Furthermore, some mitophagy-inducing substances activate biogenesis (e.g. resveratrol and metformin). Finally, we discuss the possibility of combining mitophagy and biogenesis enhancers for future treatment. In conclusion, this article provides an up-to-date source of information about natural and synthetic substances that activate mitophagy and, hopefully, stimulates new hypotheses and studies that promote healthy human aging worldwide.

Open Access Paper:

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#2

It doesn’t appear that any substance is very good at promoting Mitophagy, or am I misreading the results?

#3

In the paper of these molecules only Sodium Butyrate is identified as an HDACi, but quite a few of them are.

#4

Dietary Mitophagy Enhancer: A Strategy for Healthy Brain Aging?

Here’s more on the mitophagy topic. This one speaks to diets (Mediterranean and Okinawan) and food types to augment mitophagy to improve health and longevity.

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#5

Inflammation and mitophagy are mitochondrial checkpoints to aging

Cellular and organismal aging have been consistently associated with mitochondrial dysfunction and inflammation. Accumulating evidence indicates that aging-related inflammatory responses are mechanistically linked to compromised mitochondrial integrity coupled with mtDNA-driven CGAS activation, a process that is tonically inhibited by mitophagy.

Summary: Mitophagy = Good.

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http://www.nature.com/articles/s41467-024-47840-1

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#6

β-hydroxybutyrate exposure restores mitochondrial function in skeletal muscle satellite cells of critically ill patients.

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