This blog post examines the impact of autophagy mechanisms on aging and Parkinson’s disease treatment, exploring how modern medicine utilizes this process.
On October 3, 2016, Yoshinori Ohsumi, Professor Emeritus at Tokyo Institute of Technology, Japan, was awarded the Nobel Prize in Physiology or Medicine for his discovery of the autophagy mechanism. Professor Yoshinori Ohsumi, the 25th Japanese Nobel laureate, is known to have dedicated 50 years to autophagy research. His achievements in this field had already earned him prestigious awards. Having received the Japan Academy Prize in 2006, the Kyoto Prize in 2012, the Keio Medical Award in 2015, and the Wally Prize in 2016, he further solidified his standing as a world-class scientist. So, what is the importance and significance of autophagy in the advancement of modern medicine that has drawn such intense attention from the scientific community?
First, autophagy, as the term “self-digestion” suggests, refers to a natural degradation mechanism within cells that breaks down unnecessary or non-functional cellular components. In other words, autophagy is the system by which cells destroy and recycle their own unnecessary components to survive. This plays a crucial role in how cells maintain life through metabolism. When cellular organelles—such as mitochondria that produce energy or liposomes that store and transport substances—become damaged, unusable, or less efficient, other organelles called autophagosomes and lysosomes break them down. Our cells contain various membrane structures with diverse functions. All these membrane structures, including the cell membrane, are composed of the same materials and in the same way, allowing highly flexible material exchange between them. Autophagosomes and lysosomes are also among these intracellular membrane structures. When autophagosomes engulf aged, useless components, they fuse with lysosomes, which possess digestive enzymes, to facilitate degradation. To simplify this concept, autophagosomes can be likened to garbage trucks transporting waste, while lysosomes function like incinerators that burn that waste.
In 1988, Professor Yoshinori Ohsumi established his own laboratory and began focusing on protein degradation within the vacuole, the yeast equivalent of the lysosome in human cells. He conducted autophagy research using yeast cells, which are easy to study and commonly used as a model for human cells. Yeast is particularly useful for identifying the gene sequences governing specific intracellular activities. However, Professor Yoshinori Ohsumi encountered a major obstacle: yeast cells are too small to even determine if autophagy occurs within them. To address this, he hypothesized that artificially disrupting degradation within lysosomes would cause autophagosomes to accumulate around lysosomes, and these clustered autophagosomes would be easier to observe under a microscope. To implement this, Professor Yoshinori Ohsumi induced mutations in yeast protein degradation genes to block lysosomal protein degradation. He then starved the yeast cells of nutrients to induce autophagy. As a result, Professor Yoshinori Ohsumi observed lysosomes filling with small vesicles corresponding to autophagosomes, proving autophagy occurred in yeast cells. This discovery marked a crucial turning point in autophagy research, enabling Professor Yoshinori Ohsumi to successfully identify the gene sequences involved in the autophagy process using yeast. This research profoundly influenced subsequent studies on autophagy, leading to significant advances in modern physiological and medical research.
Autophagy breaks down unnecessary intracellular materials, enhancing metabolic efficiency and supplementing deficient nutrients. Since most of these unnecessary materials are aged cellular organelles, understanding autophagy plays a crucial role in finding solutions to human aging and its associated problems. In particular, autophagy holds a key to treating Parkinson’s disease. Parkinson’s disease occurs when excessive nitric oxide binds to the Parkin protein, preventing it from functioning properly. It has been revealed that autophagy does not occur for Parkin proteins that have lost their function. Professor Yoshinori Ohsumi’s research enabled the understanding and analysis of autophagy at the genetic level. Consequently, humanity has taken a significant step closer to solving various autophagy-related diseases like Parkinson’s disease. This achievement is highly regarded as a major contribution to the advancement of human physiological medicine.
Autophagy research is not limited solely to disease treatment. The process by which autophagy removes unnecessary components within cells also provides crucial clues for addressing aging-related issues occurring throughout the body. For example, if useless substances within cells are not removed, this can impair cell function and accelerate aging throughout the body. Given that the autophagy mechanism contributes to suppressing such aging and maintaining cellular health, it is expected to play a vital role in future research on anti-aging and lifespan extension. Thus, autophagy stands as a core mechanism for survival and regeneration at the cellular level, establishing itself as a powerful tool capable of addressing various challenges facing modern medicine. Professor Yoshinori Ohsumi’s research has made significant contributions to realizing the potential of autophagy, and his Nobel Prize win represents worldwide recognition of this achievement.
