Precision Nutrigeroscience: Nutrition for Longevity and Brain Health

The pursuit of extended lifespan and improved health requires a deep understanding of the complex interplay between our diet and unique biological factors. 

This is where precision nutrigeroscience emerges as a transformative approach, leveraging the power of biomarker identification and analysis to tailor dietary interventions. It embraces the diversity of human physiology, acknowledging that what works for one may not work for another, especially when it comes to nutrition.

The varying impact of carbohydrates and fats on mortality is a testament to this complexity. Meat intake is linked to higher life expectancies, but the impact of carbohydrates and fats varies among individuals. While some thrive on higher carbohydrate diets, others may benefit from reduced carb intake. Similarly, the type of fats consumed (animal vs. plant-based) plays a significant role in health outcomes. The goal of precision nutrigeroscience is to decipher these individual needs and craft dietary recommendations that align with each person's unique biological makeup.

Two key concepts critical to this field are oxidative stress and the retromer complex, both pivotal in understanding aging and dietary influences.

In simple terms, oxidative stress is like rusting but occurring inside our bodies. It happens when there's an imbalance between free radicals (unstable molecules that can damage cells) and antioxidants (molecules that neutralize free radicals). Just as rust can weaken metal, oxidative stress can damage our cells, DNA, and proteins, contributing to aging and diseases like Alzheimer's and Parkinson's. It's a bit like internal wear and tear. The OXR1 gene plays a crucial role here; it's like an internal 'rust-proofing' system, helping to protect our cells from this oxidative damage.

The retromer complex can be thought of as a recycling and delivery service within our cells. It ensures that proteins are properly transported and recycled in our cells, which is vital for maintaining healthy cell function, especially in neurons - the cells in our brain. When this complex doesn't work correctly, it's like a delivery service losing packages or sending them to the wrong address, leading to cell malfunction and contributing to neurodegenerative diseases. OXR1 maintains the stability of the retromer complex, protecting it from proteosomal degradation and regulating transcription of its subunits.  

Recent studies shed light on how dietary restriction (DR) influences these processes. DR, long revered for its potential to extend lifespan, does more than just limit calorie intake; it seems to fine-tune our body's response to oxidative stress and helps maintain the efficiency of the retromer complex. However, not everyone responds to DR in the same way due to genetic variations like those in the OXR1 gene, highlighting the importance of personalized nutrition.

OXR1, a gene critical for oxidative stress resistance, is linked to various neurological diseases. Dietary restriction slows brain aging by the action of mtd/OXR1 in maintaining the retromer. OXR1's influence on the retromer complex, vital for protein recycling and neuronal function, sheds light on the intricate mechanisms by which dietary restriction may slow brain aging. This discovery, rooted in extensive genetic and cellular research, including studies on patients with OXR1 mutations, opens up new possibilities for combating age-related diseases like Alzheimer's, Parkinson's, and Huntington's. By exploring the intersection of genetics, nutrition, and aging, precision nutrigeroscience is poised to revolutionize our understanding of diet's role in health and longevity, offering personalized dietary strategies tailored to individual needs and genetic makeup.


REFERENCES

You W, Henneberg R, Saniotis A, Ge Y, Henneberg M. Total meat intake is associated with life expectancy: A cross-sectional data analysis of 175 contemporary populations. International Journal of General Medicine. 2022 Feb 22:1833-51.

Evaluating the beneficial effects of dietary restrictions: A framework for precision nutrigeroscience - PMC (nih.gov)

Researchers find gene that is necessary for lifespan extension and neuronal benefits provided by dietary restriction : science (reddit.com)

Wilson KA, Chamoli M, Hilsabeck TA, Pandey M, Bansal S, Chawla G, Kapahi P. Evaluating the beneficial effects of dietary restrictions: A framework for precision nutrigeroscience. Cell Metab. 2021 Nov 2;33(11):2142-2173. doi: 10.1016/j.cmet.2021.08.018. Epub 2021 Sep 22. PMID: 34555343; PMCID: PMC8845500.

Wilson, K.A., Bar, S., Dammer, E.B. et al. OXR1 maintains the retromer to delay brain aging under dietary restriction. Nat Commun 15, 467 (2024). https://doi.org/10.1038/s41467-023-44343-3

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