Beclin-1 Mutant Mice Live 10% Longer Due to Enhanced Autophagy

Autophagy is the name given to a collection of cellular housekeeping processes responsible for recycling damaged or unwanted proteins and cellular structures, preventing them from causing further harm within the cell. Many of the methods of modestly slowing aging in laboratory species are observed to involve increased levels of autophagy. For some, such as calorie restriction, there is evidence to demonstrate that functional autophagy is required for aging to be slowed.

Researchers have long been interested in developing pharmaceutical means to enhance autophagy as a form of therapy. This is arguably even more the case these days, now that treating aging as a medical condition is considered to be a respectable goal. Despite the many years of work, therapeutic enhancement of autophagic processes has yet to progress all that far the laboratory, however. Trials have been conducted, but reliable, safe autophagy enhancing drugs have yet to emerge at the far side. The research here is one of many examples in which researchers identify a possible target mechanism for further development.

Researchers 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. Specifically, they have about a 10 percent extension in lifespan and are less likely to develop age-related spontaneous cancers and age-related pathological changes in the heart and the kidney.

Twenty years ago, researchers 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, the team found that the genetic machinery required for autophagy was essential for the lifespan extension observed in long-lived mutant roundworms. "Since then, it has become overwhelmingly clear that autophagy is an important mechanism necessary for the extended lifespan that is observed when model organisms are treated with certain drugs or when they have mutations in certain signaling pathways. The body's natural ability to perform autophagy declines with aging, which likely contributes to the aging process itself."

Yet 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, researchers 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. "The results suggest that it should be safe to increase autophagy on a chronic basis to treat diseases such as neurodegeneration. Furthermore, they reveal a specific target for developing drugs that increase autophagy - namely the disruption of Beclin 1 binding to Bcl-2."



Intuitively , autophagy should be good for the body. What are the downsides? Eating away perfectly good organelles while not producing enough new ones? Wasting too much energy on that? Slowing down the growth?

It would be interesting to have a study where the autophagy levels can be regulated , especially with some kind of external switch.
And let's try different levels up to outright mortality. The upregulate it at different ages and different level of radiation and Chemical existe/damage

Posted by: Cuberat at May 31st, 2018 7:25 AM

Many elderly people have trouble sleeping more than 3 or 4 hours a night. I wonder whether or not this potential autophagy enhancing wonder drug could solve this sleeping problem as well.

Posted by: Biotechy Marcks at May 31st, 2018 7:50 AM

I apologize for this somewhat off-topic spam, but I'm not sure where else to post it, as there hasn't been any discussion recently of charities here. Feel free to delete this post if it is inappropriate.

In January, when that Pineapple Fund donation of $1m was announced, I discussed how the Prohashing mining pool ( was going to add support to allow cryptocurrency mining to charity. We finished the implementation and plan to release this feature before June 12. Once released, miners will set a percentage of their profits to go to specific charities, and the donations will be paid automatically to the charity's (LTC/BCH/other chain with low fees) address every day.

I posted a call for charity nominations at and definitely want medical research to be at the top of the list. Reason suggested the SENS Foundation, and I was hoping that others here might be willing to post here or at that topic with suggestions of other charities in this field that have low overhead and good management. As the post indicates, banks keep closing our accounts as happens to everyone who buys or sells significant amounts of cryptocurrency, and we can't afford the man hours to convert cryptocurrencies to dollars. We can only donate to charities that will accept coins.

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Posted by: Steve Sokolowski at May 31st, 2018 7:58 AM

the latest post at my entry into life extension and supporting it were after I were transplanted. I think most people that are transplanted get it Bec its a radical procedure vs vaccination ex. therefore I think increasing the availability of organs will make more people get the idea. most people around transplanted patients also get it. therefore I think the best way to use funds are to donate to organ preservation alliance bec better cryopreservation will make use of the 60-70% of organs not used which are donated. this year $ 250.000 are matched.

Posted by: Gekki at May 31st, 2018 11:29 AM

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