Cellular Recycling Process is Key to Longer, Healthier Life

Source: UT Southwestern Medical Medical Center

Summary: Building on two decades of research, investigators at UT Southwestern have determined that “cellular housekeeping” can extend the lifespan and healthspan of mammals.

Twenty years ago, Dr. Levine and her colleagues discovered beclin 1 – a key gene in the biological process of autophagy. The group’s research has since shown that autophagy is important in many aspects of human health, such as preventing neurodegenerative diseases, combating cancer, and fighting infection. In 2003, Dr. Levine’s team found that the genetic machinery required for autophagy was essential for the lifespan extension observed in long-lived mutant roundworms. A study jointly led by Drs. Salwa Sebti and Álvaro Fernández, postdoctoral researchers in the Center for Autophagy Research at UT Southwestern found that mice with persistently increased levels of autophagy, the process a cell uses to dispose of unwanted or toxic substances that can harm cellular health – live longer and are healthier. The study findings were published in the journal Nature.

Natural, regulated, destructive mechanism of the cell

The UTSW research team that reported on autophagy in Nature includes, from left: (front) Drs. Ming Chang Hu, Beth Levine, and Orson Moe, and (back) Salwa Sebti and Álvaro Fernández. Credit: UT Southwestern

A crucial question remained unanswered: Is increased autophagy throughout mammalian life safe and beneficial? In other words, can autophagy extend lifespan and improve healthspan? To answer this question, Dr. Levine and her UTSW colleagues created a genetically engineered mouse that had persistently increased levels of autophagy. The researchers made a mutation in the autophagy protein Beclin 1 that decreases its binding to another protein, Bcl-2, which normally inhibits Beclin 1’s function in autophagy. As the researchers expected, these mice had higher levels of autophagy from birth in all of their organs. Based on the results reported, drugs acting through this mechanism might be expected to improve the health and prolong the lifespan of human beings.

Dr. Beth Levine said, “These studies have important implications for human health and for the development of drugs to improve it.”

More Information: Álvaro F. Fernández et al, “Disruption of the beclin 1–BCL2 autophagy regulatory complex promotes longevity in mice”, Nature (2018). DOI: 10.1038/s41586-018-0162-7 

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