. Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice. Nature. 2018 May 30; PubMed.

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  1. Age-related diseases, such as Alzheimer’s disease, have become a major medical and societal challenge in recent decades. Thus, it is necessary to pursue a way to improve both lifespan and healthspan of the aged populations. The work from Dr. Beth Levine’s lab, at the University of Texas Southwestern Medical Center, Dallas, showed that enhancing a cellular self-cleaning and recycling pathway can prolong longevity. This pathway, called autophagy (literally as “self-eating”), removes damaged and toxic proteins and is regulated by an interaction between the autophagy protein Beclin 1 and its inhibitor BCL2. Under stress conditions, Beclin 1 is released from BCL2 and autophagy is induced. They used a genetically engineered mouse model containing a single mutation in Beclin 1 that blocks the inhibitory Beclin 1-BCL2 binding and leads to high autophagy spontaneously in multiple tissues, including muscle, heart, kidney, and liver. The work demonstrated that autophagy induction in these mice leads to a prolonged lifespan and an overall improved healthspan, including delayed cardiac aging, delayed renal aging, and reduced tumorigenesis. In a related work from my lab published last year, we used the same mouse model and showed that this Beclin 1 mutation can also click on autophagy in the brain. We found that high autophagy caused by this mutation reduced toxic AD-associated amyloid peptides, and improved survival and cognitive function in Alzheimer’s disease mice (Rocchi et al., 2017). Together, these findings clearly demonstrate that enhancing autophagy is an effective method to promote healthier aging.

    Overall, this is a very important finding suggesting that restoring “self-cleaning and housekeeping” (autophagy) is likely a promising new strategy to delay aging and ameliorate age-related conditions, especially when recent studies suggest autophagy dampens during aging. Given starvation and physical exercise are two effective physiological methods to activate autophagy, the research implies that autophagy induction may be an underlying mechanism mediating the anti-aging benefits of caloric restriction and exercise recently reported in humans and in research animals.

    References:

    . A Becn1 mutation mediates hyperactive autophagic sequestration of amyloid oligomers and improved cognition in Alzheimer's disease. PLoS Genet. 2017 Aug;13(8):e1006962. Epub 2017 Aug 14 PubMed.

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