Plant compounds “delay aging” through molecular mechanisms, review highlights

04 Jul 2023 --- China-based researchers reviewed the use of natural products, containing polyphenols, saponins, alkaloids and polysaccharides, as potential anti-aging agents by highlighting the nutrient-sensing pathways these products influence for their health effects.

Although there’s a growing understanding of biological mechanisms involved in aging among scientists, including the most prominent genes and enzymes involved, the authors note that delaying and deterring aging-related diseases in humans is limited.

“The research acknowledges the urgent global health challenge posed by the rising burden of aging-related diseases and the potential benefits of natural products in treating these conditions,” note the authors. 

“Dietary supplements and natural products can delay the development of aging by mitigating cell proliferation, DNA damage, oxidative stress, inflammation and activating cell autophagy and mitochondrial homeostasis.” 

Cellular pathways mediate anti-aging effects 
Nutrient-sensing pathways are the primary cellular pathways to mediate anti-aging effects of natural products. The study, published in Frontiers in Nutrition, notes that IIS, mTOR, AMPK and SIRT1 signaling pathways modulate aging by interacting with each other. 

The researchers reviewed anti-aging benefits of polyphenols, saponins, alkaloids and polysaccharides.Over time, these longevity mediators break down, which disrupts metabolic health and leads to cardiovascular and metabolic disorders. 

The IIS pathway connects nutrient levels to metabolism, growth, development, longevity and behavior. SIRT1 plays an essential anti-inflammatory role, while p53 proteins regulate pathways involved in the cell cycle, apoptosis and metabolism. 

AMPK regulates cell growth and proliferation and plays a vital role in cellular energy metabolism. Its decline has been associated with aging and can contribute to the onset of age-related diseases. 

mTOR is a protein kinase that regulates cellular processes such as cell growth, cycle and survival. Inhibiting the mTOR pathway promotes autophagy – a process by which a cell breaks down old, damaged or abnormal proteins and other substances to be recycled for other cell functions. 

Preventing aging-related diseases 
According to the researchers, polyphenols have antioxidant, anti-inflammatory and anticancer properties, which can help to prevent aging-related diseases. For example, a clinical study found that a botanical blend, high in polyphenols, provides anti-aging benefits for the skin.

Polyphenols include flavonoids, phenolic acids, stilbenes and lignans. These plant compounds are commonly found in fruits, vegetables, grains, coffee and tea. 

The researchers note that the stilbene resveratrol is the most studied natural product with anti-aging effects. The compound has been reported to have anticancer effects in medicinal plant screening.  

Literature finds that the compound regulates apoptosis (programmed cell death), inhibits inflammation, suppresses oxidative stress, regulates the gut microbiome and improves mitochondrial function by modulating specific signaling pathways. 

Several plant compounds have antioxidant and anti-inflammatory properties that can help to prevent aging-related diseases.According to the researchers, quercetin, the most widely studied flavonoid, is seen as an anti-aging compound due to its long-term anti-inflammatory properties and its antioxidant and antimicrobial activities. 

In earlier research, the compound was found to alleviate aging in mesenchymal stem cells and inhibit the proliferation of colorectal cancer cells. However, its effectiveness varies with doses and experimental conditions. 

Pharmacological effects of alkaloids  
The researchers suggest that alkaloids are among the most important classes of natural products as they exhibit significant pharmacological effects. Examples include morphine, quinine, capsaicin and caffeine. 

Alkaloids have potent antioxidant, anti-inflammatory and neurotrophic effects and could be effective against aging and age-related diseases. For example, research is underway on whether caffeine can reduce cognitive impairment in age-related disorders. 

However, the authors note more studies are needed to prove alkaloids’ efficacy and potential side effects. 

The authors also identify anti-aging activities for several polysaccharides and their bioactive substances. These plant compounds can help prevent chronic diseases and delay aging by reducing oxidative damage and inflammatory effects and inhibiting telomere shortening. 

For example, cordyceps polysaccharides may extend the life of fruit flies by increasing the functioning of antioxidant genes. 

Natural sources of saponins, found in plants like ginseng and licorice, are also used in herbal and traditional medicine. However, the researchers note their bioavailability after consumption is relatively low. It is also challenging to separate saponins from nature. 

Missing information and research  
The authors caution that current research on the therapeutic effects of natural products in anti-aging is primarily based on laboratory studies. In contrast, epidemiological studies and clinical trials still need to be included.

Clinical trials and epidemiological studies are key to assess product safety and efficacy.How specific anti-aging molecules in natural products work together also remains unclear. 

Moreover, the researchers note that effective and safe doses still need to be determined. A crucial challenge for developing natural products as anti-aging agents are the low contents of effective components and oral bioavailability. 

Further research is needed to increase the number of large and well-controlled clinical trials to determine natural products’ safety, efficacy and tolerability and understand the effects of known and unknown anti-aging plant compounds. 

In terms of limitations, the authors note there needs to be more in-depth analysis of individual compounds and their specific effects on aging-related pathways. 

“Another limitation is that the review primarily focuses on cellular and molecular mechanisms and does not address broader issues such as regulatory, economic and social barriers to using natural products as a viable treatment option for aging-related diseases.”

By Jolanda van Hal