Protein Homeostasis and Antiaging Medicine: Autophagy and Antiaging

Macroautophagy (hereafter referred to as autophagy) is a large-scale degradation system that exists universally in eukaryotes. Autophagy is always occurring at low levels within our body’s cells, but it is strongly induced when cells detect starvation or various stresses. When autophagy is induced, a double-membrane structure called an autophagosome is created within the cell, which surrounds molecules and structures in the cytoplasm. The autophagosome then fuses with a lysosome, which contains a variety of hydrolytic enzymes, and the enclosed components are degraded and recycled (Fig. 22.1). Autophagy was traditionally thought of as a nonselective degradation system, but today it is known to exist as selective autophagy, which selectively removes organelles such as mitochondria, lysosomes, and endoplasmic reticulum (ER), aggregation-prone proteins, and invading bacteria. The membrane dynamics and molecular mechanisms of autophagy remained unclear for a long time, but the identification of a series of autophagy-related genes (ATG) through genetic analysis using yeast was a breakthrough, and the field has rapidly expanded over the past 30 years. Many reviews have been published on the detailed control mechanisms of autophagy, and readers are referred to these [1]. Through analysis so far, it has been found that autophagy not only secures necessary nutrients during starvation, but also plays a role in cellular metabolism and removal of harmful substances, and various physiological functions due to these actions are being revealed one after another. Below, I will introduce the involvement of autophagy in aging and lifespan control, which has become clear in recent years, and the potential for antiaging by autophagy.