In a groundbreaking discovery, recent research sheds light on the significant impact of dietary restriction on brain health and aging, attributing a pivotal role to the OXR1 gene. This gene emerges as a key player in extending lifespan and ensuring healthy brain aging, particularly in response to dietary restriction.
The study, involving extensive research on fruit flies and human cells, underscores the importance of the OXR1 gene in preserving neuronal protection and retromer function—a complex vital for recycling cellular proteins. These findings pave the way for potential therapeutic interventions targeting age-related neurodegenerative diseases and strategies for extending lifespan.
Key findings include:
1. The OXR1 gene is crucial for the benefits of dietary restriction, specifically impacting brain health and aging.
2. OXR1 influences the retromer complex, crucial for recycling cellular proteins, and plays a vital role in neuronal function and health.
3. The research, conducted on fruit flies and human cells, suggests potential new treatments for neurodegenerative diseases and strategies for healthy aging.
Caloric restriction is recognized for its positive impact on health and longevity, but its effects on brain protection have remained largely mysterious. The research team at Buck Institute unraveled a connection to the OXR1 gene, essential for both dietary restriction-induced lifespan extension and healthy brain aging.
Kenneth Wilson, a Buck postdoc and the study's first author, highlighted the significance of understanding how dietary restriction affects the brain, challenging common perceptions focused on the digestive tract or fat buildup. The team's findings revealed that the OXR1 gene is vital in the brain, marking a crucial resilience factor against aging and neurological diseases.
The study delves into the cellular mechanism underlying how dietary restriction can delay aging and slow the progression of neurodegenerative diseases. By exploring this mechanism in fruit flies and human cells, the researchers identified potential therapeutic targets for combating aging and age-related neurodegenerative diseases.
Pankaj Kapahi, co-senior author and Buck Professor, emphasized a neuron-specific response responsible for the neuroprotection observed with dietary restriction. Strategies like intermittent fasting or caloric restriction, limiting nutrients, may enhance the levels of the OXR1 gene, mediating its protective effects.
Lisa Ellerby, co-senior author and Buck Professor, emphasized OXR1 as a crucial brain resilience factor against aging and neurological diseases.
The study aims to understand the variability in responses to dietary restriction, considering the diverse reactions observed across individuals and tissues. By scanning different genetic backgrounds in fruit flies, the team identified the OXR1 gene as a promising candidate.
OXR1's role in protecting cells from oxidative damage, its influence on the retromer complex, and its association with age-related neurodegenerative diseases were key revelations. The study's in-depth tests unveiled a detailed picture of how OXR1, through the retromer pathway, slows brain aging.
The research also opens the door to exploring compounds that increase OXR1 levels during aging to delay brain aging. The prospect of extending lifespan through excess OXR1 expression in humans is an intriguing avenue for further investigation.
In conclusion, the study underscores the far-reaching impact of diet on overall bodily processes, urging support for healthy eating habits. The potential therapeutic avenues identified in this research may contribute to understanding and addressing the underlying causes of brain degeneration.
Researchers involved in the study include Sudipta Bar, Enrique Carrera, Brian Hodge, Tyler Hilsabeck, Joanna Bons, George Brownridge III, Jennifer Beck, Jacob Rose, Melia Granath-Panelo, Christopher Nelson, Grace Qi, Akos Gerencser, Jianfeng Lan, Rachel Brem, and Birgit Schilling.
The work received support from the National Institutes of Health (NIH), the Larry L. Hillblom Foundation, and the National Centers of Competence in Research (NCCR). Pankaj Kapahi disclosed being a founder and a member of the scientific advisory board at Juvify Bio, with no conflicts of interest reported by other authors.