Can caloric restriction supplements mimic fasting? | Dr. Mark Mattson
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Scientists have identified various bioactive compounds that mimic some of the ways in which calorie restriction or fasting work. The best-studied of these so-called mimetics include resveratrol, a polyphenol found in grapes and wine, and spermidine, a polyamine compound found in cheese and mushrooms. A mimetic that Dr. Mattson has worked with is 2-deoxyglucose – a glucose molecule that lacks a hydroxyl group. 2-deoxyglucose can be taken up in cells just like glucose is, but it cannot be used to produce ATP. Consumption of 2-deoxyglucose mimics the effects of glucose deprivation. Although some research indicates that 2-deoxyglucose is neuroprotective and extends lifespan, it appears to have harmful effects on the cardiovascular system. Dr. Mattson cautions against relying on mimetics; rather he recommends exercising, fasting, eating a healthy diet, and keeping the brain engaged as the best strategies for maintaining cognitive health. In this clip, Dr. Mark Mattson discusses the pros and cons of calorie restriction mimetics.
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A family of proteins produced by cells in response to exposure to stressful conditions. Heat shock proteins are expressed in response to heat as well as exposure to cold and UV light, and during wound healing and tissue remodeling. Many heat shock proteins function as chaperones by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by cell stress. A 30-minute 73ºC sauna session in healthy young adults has been shown to cause a robust and sustained increase in the production of heat shock proteins for up to 48 hours afterward.[1]
A precursor molecule for the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a coenzyme that participates in the production of cellular energy and repair. NMN helps maintain cellular levels of NAD+, thereby facilitating NAD+-dependent cellular activities, such as mitochondrial metabolism, regulation of sirtuins, and PARP activity. Animal studies have demonstrated that NMN administration is effective in increasing NAD+ levels across multiple tissues while improving the outcome of a variety of age-related diseases. Although NMN administration has proven to be safe and to effectively increase NAD+ levels in rodents, the safety and efficacy of NMN supplementation in humans remain unknown. NMN is available in supplement form and is present in various types of food, including broccoli, avocado, and beef. It is also an intermediate compound in the NAD+ salvage pathway, the recycling of nicotinamide into NAD+.
A compound initially developed as an antifungal agent. This use was abandoned, however, when it was discovered to have potent immunosuppressive and antiproliferative properties due to its ability to inhibit one of the complexes of mTOR (mTORC1). Rapamycin has since shown interesting lifespan extension properties in animals.
A polyphenolic compound produced in plants in response to injury or pathogenic attack from bacteria or fungi. Resveratrol exerts a diverse array of biological effects, including antitumor, antioxidant, antiviral, and hormonal activities. It activates sirtuin 1 (SIRT1), an enzyme that deacetylates proteins and contributes to cellular regulation (including autophagy). Dietary sources of resveratrol include grapes, blueberries, raspberries, and mulberries.
Resveratrol Autophagy ↑ Deacetylases (especially SIRT1) → ↓ Protein Acetylation → Autophagy
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