Scientists Determine How Resveratrol Could Combat Multiple Chronic Diseases

Resveratrol — a natural molecule found in red wine — could potentially combat age-related conditions like neurodegeneration, heart disease, and cancer by improving mitochondrial health.

Key Points:

A common link between Alzheimer’s disease, Parkinson’s disease, stroke, heart disease, obesity, arthritis, and cancer is dysfunctional mitochondria.
Various studies show that resveratrol optimizes the function of mitochondria in models of these diseases, suggesting it could potentially prevent or treat them in humans.

The so-called powerhouse of the cell — mitochondria — tends to become less of a powerhouse with aging. Consequently, dysfunctional mitochondria are an underlying characteristic of chronic conditions like Alzheimer’s disease, muscle weakness, heart disease, and cancer. It follows that optimizing mitochondrial health could counteract these age-related conditions.

Now, scientists from the Wuhan Sports University in China have examined the role of resveratrol — a compound found in many foods — in optimizing mitochondrial health. In their review, published in Food Science and Human Wellness, Tao and colleagues conclude that resveratrol enhances mitochondrial function, combating multiple age-related conditions. While this appears to be the case for animal and cell models, the same could hypothetically be true for humans.

Resveratrol Could Treat or Prevent Age-Related Diseases

Tao and colleagues say that current drugs can target specific aspects of mitochondria, but they cannot optimize mitochondrial quality. On the other hand, exercise can improve mitochondrial quality and it seems possible that consuming a diet rich in plant-based compounds like resveratrol could do the same.

Found in plants such as grapes, mulberries, soybeans, and peanuts, resveratrol is a naturally occurring compound called a polyphenol that has been noted for its anti-aging properties. It’s been shown to counter mitochondrial dysfunction — a hallmark of aging which is considered a limiting factor of lifespan. Thus, by revitalizing mitochondria, resveratrol could prevent or treat multiple age-related diseases, such as the diseases summarized here.

Alzheimer’s Disease (AD)

AD is a neurodegenerative disease that leads to changes in learning, memory, emotion, and behavior. In AD, mitochondria produce excessive levels of molecules called reactive oxygen species (ROS) that cause damage to cells. This leads to cell death and contributes to brain degeneration.

Treatment with resveratrol has been shown to improve mitochondrial function in AD by reducing ROS levels. Resveratrol also activates the clearance of damaged mitochondria through a process called mitophagy. In turn, the removal of damaged mitochondria allows healthy mitochondria to function more efficiently and produce less ROS.

(Tao et al., 2023 | *Food Sci. Hum. Wellness*) **Resveratrol in Alzheimer’s Disease.** Resveratrol promotes autophagy of mitochondria (mitophagy) and reduces reactive oxygen species (ROS), partly via a mitochondrial protein called COXIV, to counteract damaged mitochondria.

Parkinson’s Disease (PD)

PD is a neurodegenerative disease that leads to trembling-like movements called tremors, as well as rigid movements and mental abnormalities. In models of PD, mitochondrial impairments trigger low levels of cellular energy — ATP.

However, resveratrol can increase newborn mitochondria, which reduces ROS and increases ATP levels. Additionally, similar to AD, resveratrol activates mitophagy in PD. Furthermore, studies show that resveratrol can reduce the death of neurons and potentially mitigate neurodegeneration by diminishing ROS levels.

(Tao et al., 2023 | *Food Sci. Hum. Wellness*) **Resveratrol in Parkinson’s Disease.** Resveratrol promotes mitophagy and the production of new mitochondria (mitochondrial biogenesis) by activating molecules like AMPK, SIRT1, and PGC-1⍺, which increases ATP production. It also reduces ROS levels to reduce cell death (apoptosis).

Stroke

Stroke occurs when blood vessels in the brain become blocked or ruptured, leading to brain cell death. Resveratrol can limit brain cell death by improving the fusion of mitochondria. Through this fusion process, damaged mitochondria fuse together with healthy mitochondria, which revives the damaged mitochondria.

Mitochondrial fusion is initiated by a longevity-associated molecule called AMPK. AMPK is considered a longevity molecule because it is activated in response to caloric restriction (CR) — eating less calories without malnourishment. CR is associated with longevity because it has been shown to prolong the lifespan of rodents more reliably than any other intervention.

In addition to promoting mitochondrial fusion via activation of AMPK, resveratrol also reduces ROS levels in animal models of stroke. It achieves this, in part, by boosting the cell’s natural antioxidant defense systems. Moreover, by counteracting damage caused by excessive levels of ROS, resveratrol protects brain cells from death.

(Tao et al., 2023 | *Food Sci. Hum. Wellness*) **Resveratrol in Stroke.** Resveratrol triggers mitochondrial fusion via AMPK and Mfn1 molecules and reduces cell death (apoptosis) by increasing antioxidant defenses (GSH), increasing mitochondrial health (MMP), reducing ROS (H₂O₂), and blocking a mitochondria-mediated cell death pathway (Lox-1 to Bax to Cyt-C to Caspases).

Muscle Loss

Similar to the tendency of the brain to degenerate in an age-dependent manner, so too does muscle. Known as sarcopenia, aging leads to a progressive decline in muscle mass (atrophy) and strength (weakness). Sarcopenia is influenced by factors such as reduced protein synthesis and increased protein degradation, impaired cellular recycling (autophagy), and a reduced number of mitochondria.

Studies show that resveratrol treatment enhances mitochondrial quality by promoting mitophagy and mitochondrial fusion in muscle cells, which could potentially counteract sarcopenia. Supporting this, in a study involving Harvard’s Dr. David Sinclair, resveratrol was shown to improve mitochondrial quality by increasing the number of mitochondria in the muscles of elderly individuals.

(Tao et al., 2023 | *Food Sci. Hum. Wellness*) **Resveratrol in Muscle Loss.** Resveratrol activates mitophagy, mitochondrial fusion via Mfn2, and improves mitochondrial quality via PKA, LKB1, and AMPK molecules.

Heart Disease

Heart disease is the leading cause of death worldwide. In studies of the heart, resveratrol induces mitophagy and mitigates damage from excessive ROS levels. Additionally, resveratrol leads to the activation of sirtuins — a family of longevity-associated molecules that are also activated by CR. In blood vessel cells, resveratrol has similar effects, suggesting its potential role in combating cardiovascular diseases like artery plaque buildup (atherosclerosis) which leads to heart attacks.

(Tao et al., 2023 | *Food Sci. Hum. Wellness*) **Resveratrol in Cardiovascular Disease.** Resveratrol improves mitochondrial quality by reducing ROS levels, promoting mitophagy, and activating pathways that include the molecules SIRT1, SIRT3, Mfn2, Parkin, PGC-1⍺, DJ-1, and COX-1.

Obesity

Obesity is caused by a high ratio of calorie intake to calorie expenditure, leading to an energy surplus that is converted to fat. In turn, increased fat tissue mass leads to metabolic dysfunction. This metabolic dysfunction includes insulin resistance — when our cells don’t properly respond to insulin, causing elevated levels of glucose in the blood.

By activating sirtuins, resveratrol has been shown to prevent diet-induced obesity and insulin resistance in rodents. Additionally, resveratrol was shown to alleviate insulin resistance by improving mitochondrial function in brown fat tissue. Brown fat tissue is different from the usual white fat tissue, in that it tends to use fat molecules to produce heat rather than energy (ATP).

In elderly individuals, resveratrol was shown to block fat accumulation and promote fat loss via AMPK. Specifically, AMPK activation blocks fat synthesis and increases the metabolism of fat, which partially occurs in mitochondria. Furthermore, resveratrol combined with EGCG (epigallocatechin-3-gallate) — found in green tea — improved mitochondrial size and promoted fat metabolism in obese individuals.

(Tao et al., 2023 | *Food Sci. Hum. Wellness*) **Resveratrol in Obesity.** Resveratrol enhances mitochondrial function by activating SIRT1 and PGC-1⍺, which transforms white fat into brown fat. In turn, increased brown fat leads to reduced insulin resistance.

Arthritis

Arthritis is the inflammation of the joints, causing swelling, pain, and joint deformations. It has been reported that nearly one-third of the elderly population suffers from arthritis. With that being said, optimizing mitochondrial function with resveratrol could potentially play a role in preventing or treating arthritis and reduce overall geriatric suffering.

In addition to generating energy, mitochondria can trigger cell death. In the case of rheumatoid arthritis (RA) — an autoimmune disease — cell death can be good. This is because in RA some cells of the joint replicate too quickly and cause painful swelling. Resveratrol has been shown to cause death to these pain-inducing RA cells in laboratory dish experiments, suggesting the same could potentially occur in whole organisms.

In many cases and in the context of some diseases, cell death is not good. Typically, it causes organs and tissues to degenerate and slowly lose their function, as with neurodegeneration, muscle loss, and heart disease. To this end, studies have shown that by countering cell death mediators in cartilage cells, resveratrol could protect against joint degeneration in arthritis.

(Tao et al., 2023 | *Food Sci. Hum. Wellness*) **Resveratrol in Arthritis.** Resveratrol activates mitochondrial-mediated cell death by increasing the Cyt-C molecule and reducing mitochondrial voltage (MMP), leading to increased caspase enzymes and the death (apoptosis) of rheumatoid arthritis-related cells. In cartilage cells (chondrocytes), the opposite occurs, and cell death is blocked by resveratrol.

Cancer

Resveratrol has been shown to reduce the growth of tumors that have been surgically attached to mice. Resveratrol also reduces the growth of cancer cells by inducing mitochondrial-mediated cell death. Since our mitochondria are like batteries, resveratrol triggers cancer cell death by disrupting the mitochondrial membrane potential — the voltage difference across the mitochondrial inner membrane that is essential for energy production.

Interestingly, resveratrol appears to have the opposite effect in non-cancer cells. In cancer cells, it has been shown to increase ROS levels, leading to cell death. Additionally, while resveratrol promotes mitochondrial fusion in healthy cells, it appears to reduce mitochondrial fusion in cancer ones. Mechanistically, it is unclear how resveratrol could have opposite effects in cancer vs non-cancer cells and the topic remains a subject of investigation.

(Tao et al., 2023 | *Food Sci. Hum. Wellness*) **Resveratrol in Cancer.** Resveratrol increases ROS levels, blocks mitochondrial fusion, reduces mitochondrial voltage (MMP), and activates cell death pathways (Cyt-C and caspases) to cause death (apoptosis) to cancer cells.

The Outlook for Humans

While the positive effects of resveratrol are summarized here, the results are mostly from cell and animal models, and other studies have shown negative results. Moreover, exemplified by the cancer studies, resveratrol can have toxic effects like increasing ROS levels and triggering cell death. Additionally, it may be difficult to target mitochondria with resveratrol in humans, and there are issues with its absorption. Therefore, more studies examining the effects of resveratrol in humans will better elucidate its effects on age-related diseases.