Fountain of youth—Targeting autophagy in aging

Published on March 29, 2023

Imagine if you could uncover the secrets to staying young and healthy as you age. Well, scientists are doing just that by studying a process called autophagy. Think of autophagy as the body’s own cleaning crew, clearing out old or damaged cells to make way for new ones. It’s like when you clean out your closet and get rid of old clothes to make space for stylish new outfits. This process has caught the attention of researchers because it plays a crucial role in determining how long we live and our overall health. By stimulating autophagy in experimental models, scientists have managed to extend lifespan and improve health outcomes. However, when it comes to humans, things are a bit more complicated. Clinical trials targeting autophagy have shown mixed results, with some drugs showing promise while others fall short. To improve the effectiveness of these trials, researchers suggest using preclinical models that closely resemble humans. Additionally, they explore how cellular reprogramming techniques can be used to better understand autophagy in human-derived models such as stem cells. If you want to dive deeper into the fascinating world of autophagy and its potential role in aging, check out the full article!

As our society ages inexorably, geroscience and research focusing on healthy aging is becoming increasingly urgent. Macroautophagy (referred to as autophagy), a highly conserved process of cellular clearance and rejuvenation has attracted much attention due to its universal role in organismal life and death. Growing evidence points to autophagy process as being one of the key players in the determination of lifespan and health. Autophagy inducing interventions show significant improvement in organismal lifespan demonstrated in several experimental models. In line with this, preclinical models of age-related neurodegenerative diseases demonstrate pathology modulating effect of autophagy induction, implicating its potential to treat such disorders. In humans this specific process seems to be more complex. Recent clinical trials of drugs targeting autophagy point out some beneficial effects for clinical use, although with limited effectiveness, while others fail to show any significant improvement. We propose that using more human-relevant preclinical models for testing drug efficacy would significantly improve clinical trial outcomes. Lastly, the review discusses the available cellular reprogramming techniques used to model neuronal autophagy and neurodegeneration while exploring the existing evidence of autophagy’s role in aging and pathogenesis in human-derived in vitro models such as embryonic stem cells (ESCs), induced pluripotent stem cell derived neurons (iPSC-neurons) or induced neurons (iNs).

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