Nutritional Supplement Composition for Mimicking Calorie Restriction via NADH Reduction
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Solution Overview
Problem
Current methods to extend lifespan and improve metabolism do not effectively mimic the life-extending effects of calorie restriction without reducing calorie intake, and there is a need for compositions that can modify metabolism to increase the NAD+/NADH ratio, activating key regulators like SIR2 for life span extension.
Innovation Solution
Development of nutritional supplements based on high throughput assays in Saccharomyces cerevisiae to identify agents that lower cytosolic NADH levels and increase NAD+ levels, using naturally occurring compounds such as potato skins, turmeric, and magnesium malate, which can be administered in various forms to mimic calorie restriction without reducing calorie intake.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If calorie restriction is implemented to extend lifespan and improve metabolism, then life span is extended and oxidative stress is reduced, but calorie intake is reduced
Solution Approach 1:
The patent uses NAD+ as an intermediary substance that mediates the effects of calorie restriction. By administering NAD+ supplements, the beneficial metabolic effects (lifespan extension, oxidative stress reduction) are achieved without actually restricting calorie intake. The NAD+ acts as a mediator that triggers the same cellular responses as calorie restriction would normally produce.
Solution Approach 2:
The patent changes the biochemical parameter of NAD+ levels in the body. Instead of changing dietary parameters (calorie restriction), the invention directly modifies the NAD+ concentration parameter to achieve the desired metabolic effects. This parameter change activates SIR2 and other longevity pathways without requiring caloric reduction.
2Duration of action of stationary object
If NADH levels are lowered to activate SIR2 and extend lifespan, then life span is extended, but metabolic rate may be affected
Solution Approach 1:
The patent specifically changes the NAD+/NADH ratio parameter by administering NAD+ supplements. This parameter change activates SIR2 deacetylase which then modifies other proteins and pathways to extend lifespan. The targeted parameter change allows selective activation of longevity pathways without necessarily reducing overall metabolic rate, as the effect is mediated through specific enzymatic pathways rather than global metabolic suppression.
Data Source
AI summary
Embodiments herein relate to agents that mimic calorie restriction (CR) to extend life span, especially agents that lower the level of cytosolic NADH and increase the level of cytosolic NAD+ (relative to NADH) required to mimic calorie restriction that results in life span extension, at least in part by inhibition by NADH of SIR2, which is a key regulator of life span in both yeast and animals. NADH is a competitive inhibitor of SIR2, an NAD-requiring NAD-dependent histone deacetylase required for chromatin silencing and life-span extension. An overall reduction in NADH activates SIR2 and extends life span. The use of fluorescence measurements of NADH levels in a 96-well plate assay utilizing Baker's yeast (Saccharomyces cerevisiae) as a model to screen for agents and supplements that lower NADH levels is disclosed herein. A caloric restriction mimetic contains 1 part Mg2+ malate, 1 part turmeric and 98 parts dehydrated potato skins.