Mitochondria and Aging: The Mediterranean Diet as a Key to Longevity

Mitochondria, the powerhouses of our cells, are vital in the aging process and metabolic disorders. Their dysfunction is linked to cellular senescence, a key sign of aging. Understanding their role in aging and metabolic health is crucial for strategies to promote longevity and healthy aging.

The Mediterranean diet (MedDiet), known for its health benefits, may be key to supporting mitochondrial function and aging. It’s rich in antioxidants, healthy fats, and diverse plant-based foods. Studies show it improves mitochondrial bioenergetics and reduces oxidative stress. This could slow aging and lower metabolic disorder risks.

This article will explore mitochondria’s role in aging and metabolic disorders. We’ll look at how their dysfunction affects aging. Additionally, we’ll see how the Mediterranean diet can support mitochondrial health and longevity. This could help individuals take control of their aging process.

Key Takeaways

• MedDiet appears to have a positive influence on mitochondrial function, possibly by reducing oxidative stress and inflammation.
• Mitochondria have a significant role in human diseases, including aging, metabolic syndrome, and neuropsychiatric disorders.
• The MedDiet’s rich polyphenol content contributes to its antioxidant properties, potentially modulating mitochondrial antioxidant enzymes and reducing oxidative stress.
• Certain MedDiet components, such as chlorogenic acid, delphinidin, lycopene, and resveratrol, have demonstrated beneficial effects on mitochondrial function in various experimental studies.
• The MedDiet’s impact on gut microbiota may also contribute to its overall health benefits by influencing SCFA production and improving mitochondrial function.
• Omega-3 fatty acids, vitamin E, and monounsaturated fats present in the MedDiet also contribute to improved mitochondrial health.
• Further research is needed to confirm the findings in human subjects and to fully elucidate the intricate relationship between MedDiet, mitochondrial function, and various health outcomes.

Mitochondrial Dysfunction and Oxidative Stress

Oxidative stress occurs when the balance between free radicals and antioxidants is disrupted, leading to cellular aging and age-related diseases. Mitochondrial bioenergetics, the process of generating energy, is impaired in these conditions, worsening metabolic disorders. Grasping how mitochondrial dysfunction and oxidative stress affect aging and metabolic disorders is crucial for finding effective treatments to support healthy aging and prevent these conditions.

Mitochondria and Aging: The Impact on Longevity

Mitochondria, the cells’ powerhouses, play a crucial role in aging. As we age, they often malfunction, leading to less energy production and more oxidative stress. This can cause cellular damage, contributing to age-related diseases and shorter lives.

Linked to cellular senescence, mitochondria dysfunction means cells can’t divide or function well. This decline in ATP production hampers our cells’ energy supply. Without enough ATP, our bodies face numerous age-related challenges.

Moreover, dysfunctional mitochondria produce more free radicals, molecules that harm our cells’ components. This oxidative stress speeds up aging and raises the risk of chronic diseases like heart disease, neurodegeneration, and metabolic disorders.

Mitochondria have been increasingly recognized for their importance in both the stress response and the aging process, with current research focusing on the role of mitochondria in accelerated aging and the development of age-related diseases (Han et al., 2019). Aging itself is associated with perturbations in mitochondrial structure and function, including impaired replication, alterations in mitochondrial DNA copy number (mtDNAcn) from the third decade of life onward in several post-mitotic tissues (for example, muscle, heart, and brain), increased ROS production, mtDNA mutations, and organelle damage with resulting release of ccf-mtDNA (Lagouge and Larsson, 2013).   (Pollicino 2023)

Supporting mitochondrial health can counteract aging’s negative effects. A diet rich in antioxidants, like the Mediterranean diet, helps maintain mitochondrial function. This approach aids in cellular longevity, lowers disease risk, and extends a healthy life span.

The Mediterranean Diet: A Potential Key to Longevity

The Mediterranean diet is rich in plant-based foods, healthy fats, and has a balanced omega-3 to omega-6 fatty acid ratio. It has been thoroughly studied for its health perks. Studies reveal it boosts metabolic health, cuts down the risk of cardiovascular disease, and aids in longevity.

From a literature review conducted by Davis et al (185), it was shown that that descriptions concerning MedD are common among publications. More specifically, the major components of a MedD pattern include olive oil as the main culinary fat and the high consumption of plant-derived foods (fruit, vegetables, legumes, nuts and seeds, and whole grain cereals); the moderate intake of red wine; and the moderate consumption of seafood and dairy products, such as yogurt and cheese (185). (Kyriazis 2022)

This diet is also tied to better mitochondrial function and less oxidative stress, key to aging. The anti-inflammatory and antioxidant elements in foods like olive oil, nuts, and polyphenol-rich plants help keep mitochondria healthy. This slows down cellular aging.

Different experimental models show that components of the MD, including polyphenols, plant-derived compounds, and polyunsaturated fatty acids, can improve mitochondrial metabolism, biogenesis, and antioxidant capacity. Such effects are valuable to counteract the mitochondrial dysfunction associated with obesity-related abnormalities and can represent the beneficial feature of polyphenols-enriched olive oil, vegetables, nuts, fish, and plant-based foods, as the main components of the MD.  (Khalil 2022)

Polyphenols in the Mediterranean Diet and Their Mitochondrial Benefits

(See Kyriazis 2022 for more):

Delphinidin:

Found in large quantities in red wine.
Increases mitochondrial activity through complex IV activity and mitochondrial abundance.
Upregulates the expression of TFAM, TFB2M, and NRF1, which are critical for mitochondrial biogenesis.

Lycopene:

Found in tomatoes and other red fruits and vegetables.
In endothelial cells with VEGF-induced mitochondrial dysfunction, lycopene upregulates genes related to mitochondrial biogenesis and function, including several COX members, PGC-1α, and SIRT1.

Chlorogenic Acid:

Present in coffee beans and apples.
Stimulates SIRT1 and PGC-1α in human umbilical vein endothelial cells exposed to ox-LDL, increasing mitochondrial biogenesis and reducing mitochondrial ROS levels.

Resveratrol:

Found primarily in red wine and grapes.
Activates SIRT1 and PGC-1α, enhances mitochondrial function, and helps prevent insulin resistance and cardiac failure.

Hydroxytyrosol:

Present in olive oil.
Increases mitochondrial abundance via the AMPK signaling pathway, inducing PGC-1α, TFAM, and NRF-1.
Enhances mitochondrial activity by elevating complex I and II expression and decreasing complex V expression.

Ginger Extract:

Widely used in Mediterranean and Asian diets.
Stimulates the AMPK/PGC-1α axis in HepG2 cells and in skeletal muscle, liver, and brown adipose tissue in mice.

Increases mitochondrial abundance and the expression of OXPHOS-related proteins across various tissues.

Others:

Other polyphenols associated with the Mediterranean diet that may have a positive impact on mitochondria include:

Apigenin (4,5,7-trihydroxyflavone) is a flavonoid present in vegetables (parsley, celery, and onions), fruits (oranges), herbs (chamomile, thyme, oregano, and basil), and plant-based beverages (tea, beer, and wine) [14–16]. A previous study has shown that apigenin inhibits CD38, thus increasing NAD⁺ levels, and improving glucose and lipid homeostasis in obese mice [17]. However, there have been few reports evaluating the effect of apigenin on DKD.

Here, we show for the first time that CD38 plays a crucial role in mitochondrial oxidative stress by reducing the NAD⁺/NADH ratio and Sirt3 activity in the kidneys of type 2 diabetic rats. The NAD⁺/NADH ratio and mitochondrial anti-oxidative properties mediated by Sirt3 activation are restored by apigenin, leading to the amelioration of diabetes-induced renal injury, particularly renal tubular injury. (Ogura 2020)

Mitochondrial dysfunction is a common feature of aging, neurodegeneration, and metabolic diseases. Hence, mitotherapeutics may be valuable disease modifiers for a large number of conditions. In this study, we have set up a large-scale screening platform for mitochondrial-based modulators with promising therapeutic potential.

… Using differentiated human neuroblastoma cells, we screened 1200 FDA-approved compounds and identified 61 molecules that significantly increased cellular ATP without any cytotoxic effect. Following dose response curve-dependent selection, we identified the flavonoid luteolin as a primary hit. …

Conclusion: We provide a new screening platform for drug discovery validated in vitro and ex vivo. In addition, we describe a novel mechanism through which luteolin modulates mitochondrial activity in neuronal models with potential therapeutic validity for treatment of a variety of human diseases. (Naia 2021)

there is a growing interest in identifying safe natural compounds that enhance mitochondrial function and have limited or no side effects. Among the natural compounds, polyphenols appear to be of interest to modulate mitochondrial function. For example, resveratrol has been repeatedly shown to improve mitochondrial function and protect against metabolic diseases by activating mitochondrial biogenesis through Sirtuin 1 (SIRT1) and Peroxisome Proliferator activated receptor Gamma coactivator 1 alpha (PGC1a).3 More recently, (-)-epicatechin (EPI), a member of the flavonoids chemical family, has received attention. (Daussin 2020)

Omega-3 fatty acids (w-3 FA) have anti-inflammatory effects and improve mitochondrial function.

…The w-3 FA intervention improved mitochondrial function, mainly by decreasing nonmitochondrial respiration and increasing the reserve respiratory capacity and BHI. The intervention also reduced circulating pro-inflammatory and anti-inflammatory lymphocyte and monocytes subsets in individuals with obesity. The mitochondrial dysfunction of PBMCs and the higher proportion of peripheral pro-inflammatory and anti-inflammatory immune cells in subjects with obesity, improved with 1 month supplementation with EPA and DHA. (Borja-Magno 2023)

Summary

These findings highlight the significant role of specific polyphenols in the Mediterranean diet in enhancing mitochondrial function and biogenesis, thereby contributing to overall cellular health and metabolic regulation.

Thus, the Mediterranean diet, and particularly the polyphenols associated with that diet,  could be a key to a longer, healthier life by supporting mitochondria.

By eating foods high in omega-3 fatty acids and polyphenols, people can better their metabolic health and cardiovascular health. This could lead to a longer, more vibrant life.

Source Links

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9370259/
• https://pubmed.ncbi.nlm.nih.gov/37019345/
• https://doi.org/10.1016/j.exger.2023.112165