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Increased Autophagy Promotes Healthy Longevity in Mice

A new study suggests that autophagy, the recycling, and disposal system that cells use to remove unwanted garbage, can extend the healthy lifespan of mammals.

The study, led by Drs. Salwa Sebti and Alvaro FernΓ‘ndez from the Center for Autophagy Research, has discovered that mice with higher levels of autophagy live longer and healthier than regular mice.

This study builds on decades of research suggesting that autophagy aids longevity and that the body’s gradual, age-related loss of autophagy likely drives an aging process. However, this question has remained unanswered: “Does increasing autophagy throughout the life of a mammal increase healthy lifespan?”

In order to answer this question, the research team created special, genetically engineered mice that were designed to have more autophagy than regular mice. They achieved this by creating a mutation in the already known autophagy-associated protein Beclin 1, a protein that reduces its binding to the Bcl-2 protein, which normally inhibits the function of Beclin 1. This resulted in the mice having a higher level of autophagy from birth.

The mice in the study had around a 10% increase in lifespan and were less likely to develop age-related diseases, such as cancer and age-related, pathological changes to the heart and kidneys. They also demonstrated that increased autophagy protects the mice from the premature death that normally occurs when mice lack the longevity-associated hormone Klotho.


Autophagy increases the lifespan of model organisms; however, its role in promoting mammalian longevity is less well-established1,2. Here we report lifespan and healthspan extension in a mouse model with increased basal autophagy. To determine the effects of constitutively increased autophagy on mammalian health, we generated targeted mutant mice with a Phe121Ala mutation in beclin 1 (Becn1F121A/F121A) that decreases its interaction with the negative regulator BCL2. We demonstrate that the interaction between beclin 1 and BCL2 is disrupted in several tissues in Becn1F121A/F121A knock-in mice in association with higher levels of basal autophagic flux. Compared to wild-type littermates, the lifespan of both male and female knock-in mice is significantly increased. The healthspan of the knock-in mice also improves, as phenotypes such as age-related renal and cardiac pathological changes and spontaneous tumorigenesis are diminished. Moreover, mice deficient in the anti-ageing protein klotho3 have increased beclin 1 and BCL2 interaction and decreased autophagy. These phenotypes, along with premature lethality and infertility, are rescued by the beclin 1(F121A) mutation. Together, our data demonstrate that disruption of the beclin 1–BCL2 complex is an effective mechanism to increase autophagy, prevent premature ageing, improve healthspan and promote longevity in mammals.


It is increasingly clear that enhancing autophagy is beneficial, and this study suggests that it should be safe to consistently increase autophagy. The results suggest that improved autophagy could help to combat neurodegeneration.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
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