• Resveratrol reduces markers of senescence and inflammation in brain cells (astrocytes) from the hypothalamus — a region of the brain that may regulate the process of aging. 
  • Treatment with resveratrol activates the gene for sirtuin 1 (SIRT1), an enzyme associated with increased lifespan.

The hypothalamus controls everything from our reproductive success to our sleep-wake cycles. Scientists hypothesize that when this region of the brain becomes inflamed, our body is knocked out of homeostasis, leading to metabolic diseases like obesity, as well as aging. A new study out of the Federal University of Rio Grande do Sul in Brazil suggests that such inflammation can be reduced by the grape molecule resveratrol. 

In the latest issue of  Molecular and Cellular Biochemistry, Sovrani and colleagues tested the effects of resveratrol, known for its antioxidant, anti-inflammatory, and anti-aging properties, on cultured brain cells from aged rats. They found that treating these brain cells grown in a dish with resveratrol reduces the activation of genes and proteins associated with inflammation and senescence. Furthermore, resveratrol activated the gene for SIRT1, one of the most promising anti-aging targets.

Resveratrol Reduces Brain Cell Inflammation and Senescence 

Astrocytes are constantly mingling with neurons and other central nervous system cells (i.e. glial cells), as well as blood vessels, to make sure extracellular molecules (ions, water, neurotransmitters) are balanced and in order. However, during aging, astrocytes adopt a pro-inflammatory state, potentially leading to neurotoxicity and neuroinflammation. 

Sovrani and colleagues isolated astrocytes from the hypothalamus of 24-month-old rats (equivalent to 70 human years) and grew (cultured) them in a dish. They then added resveratrol to the dish and measured changes in gene and protein activity. The measurements suggested that, overall, resveratrol reduced inflammation. Additionally, a marker for cell senescence called p21 was reduced, suggesting a reduction in senescence.

(Sovrani et al., 2022 | Mol. Cell. Biochem.) Resveratrol Reduces Senescence and Inflammation. In astrocytes from the hypothalamus of rats, resveratrol (RSV) reduces an mRNA marker for senescence called p21 (A), and an mRNA (B) and protein (C) marker for inflammation called TNF-α.

The past few decades of aging research have brought to light a collection of molecules associated with increased lifespan and ameliorating age-related diseases. Among these molecules are SIRT1 and AMPK – an enzyme that plays key roles in cellular energy homeostasis. These molecules are activated in response to caloric restriction, the most experimentally reproducible intervention for increasing lifespan. 

Sovrani and colleagues found that while resveratrol increased SIRT1 gene activation in astrocytes from the hypothalamus of old rats, it decreased AMPK activation. This is of concern because resveratrol has previously been shown to increase AMPK in astrocytes. Thus, more studies will be needed to confirm how resveratrol affects AMPK activation in the astrocytes of the aged hypothalamus. 

(Sovrani et al., 2022 | Mol. Cell. Biochem.) Resveratrol Increases SIRT1. In astrocytes from the hypothalamus of rats, resveratrol (RSV) increases SIRT1 mRNA (left) and decreases AMPK mRNA (right).

The Brazilian researchers also looked at genes involved in aging processes other than inflammation, senescence, and longevity. For example, they found that resveratrol activates genes for antioxidant enzymes and others that control mitochondrial health. Additionally, genes for balancing glutamate were increased, suggesting a reduction in glutamate toxicity. Glutamate is a neurotransmitter that can be toxic to the brain if not properly balanced and regulated, which may underlie diseases like Alzheimer’s disease.

Combining Resveratrol with NMN 

Resveratrol is a polyphenol (plant molecule) that naturally occurs in grapes, wines, peanuts, and berries, although in small quantities. Resveratrol can also be taken in supplement form at doses associated with its anti-aging benefits. Both resveratrol and NMN have been shown to improve cognition in rats, which may be a result of reduced hypothalamic inflammation. Interestingly, it has been reported that combining NMN and resveratrol reduces NAD+ levels in the brain but increases NAD+ in organs like muscle in mice. Another curiosity, an NMN transporter in the hypothalamus is associated with slowing muscle decline. Clearly, more research is needed to determine how resveratrol and NMN affect the hypothalamus to then regulate the aging of other organs like muscle.