inflammation & autoimmunity

longevity

PON1

Can This Gene Help You Live Longer? (PON1)

Written by Mathew Eng, PharmD on September 12th, 2019

What’s the secret to a long life? Who better to study than those who live to be over 100 years old? Researchers did just that and found that centenarians have something in common: they tend to have a specific variant of the PON1 gene. Find out how your genes compare and what you can do to live a longer life.

What Is The PON1 Gene?

The PON1 gene encodes a protein that is also called PON1. The protein PON1, which is short for paraoxonase 1, is an enzyme that hydrolyzes (breaks apart) many different types of chemical bonds [R].

This ability to break down various molecules is useful for when the body needs to remove certain harmful compounds. For example, PON1 breaks apart oxidized fats that could otherwise lead to heart disease, and it can also detoxify toxic compounds called organophosphates [R, R].

The PON1 gene encodes the protein PON1, which protects the body by breaking down harmful compounds.

PON1’s Effect On Lifespan

Preliminary research has revealed that certain variations in the PON1 gene may be associated with human longevity. More specifically, the “C” allele in rs662 (also sometimes referred to as “G” or “R”) is more common in people who live extremely long compared to the other “T” allele [R].

For example, a large analysis of 11 studies including almost 6,000 people found that people over 65 years old are 16% more likely to carry the “C” allele. This increases to 44-69% when looking at individuals who are over 100 years old [R].

The evidence isn’t always clear cut, however. There are other large studies that have found no connection between rs662 and longevity, so more research is needed to say for sure [R, R].

Some studies have found the “C” allele in rs662 is more common in those who live very long lives, which suggests that PON1 may influence lifespan. Other studies have found no connection, so more research is needed.

How Could the PON1 Gene Boost Longevity?

Human longevity is complex, with many factors at play, so the relationship between genes and lifespan is not always clear. Additionally, the studies are not conclusive. But if future studies did find a link between this gene and longevity, are there any good ideas on how it may boost longevity? The short answer is yes.

Preventing Heart Disease

The PON1 protein is able to break down oxidized fats, preventing plaque buildup in the blood vessels (also known as atherosclerosis). This means PON1 may help protect against several heart disorders such as heart failure, heart attack, and coronary artery disease [R].

A recently published, comprehensive analysis of 64 studies including over 53,000 people found that people with the “C” allele have lower rates of heart attacks and coronary artery disease compared to those without it [R].

The “C” allele in rs662 is associated with lower rates of heart disease, which may explain how this allele could help you live longer.

Detoxing Harmful Toxins

Another important function of PON1 is eliminating toxins from the body. More specifically, PON1 breaks down organophosphates, a toxic compound commonly found in pesticides [R].

Variations in rs662 can also alter the detox activity of PON1. An analysis of 9 studies including over 2,000 people found that people who carry the “T” allele have higher rates of organophosphate toxicity compared to people who carry the “C” allele [R].

This detox ability is important because those who do not properly eliminate organophosphates from their body may be at a higher risk for cancer and several neurodegenerative disorders [R].

The “C” allele in rs662 is linked to a lower rates of organophosphate toxicity, which may also contribute to longevity.

Your PON1 Results for Longevity

Primary SNPs:

PON1 rs662

“C” = Longer than average lifespan, more likely to live past 100
“T” = Less likely to live past 100

Population Frequency:

33% of the world population have “CC”
Only 7.6% of people with European ancestry have “CC”

SNP Table

variant	genotype	frequency	risk allele
rs662

Recommendations

Lifestyle

There are several lifestyle changes you can make to significantly boost your PON1 activity and longevity. You should try to:

Quit smoking: the oxidant compounds in cigarettes can inhibit PON1, and smoking is well-known to shorten your lifespan [R, R]
Exercise more: it activates PPAR-gamma, a receptor that increases PON1 expression; regular exercise by itself is also shown to decrease the risk of death [R, R, R, R]
Fix any inflammation issues: inflammatory compounds like IL-1b and TNF-alpha can reduce the expression of PON1 while also reducing life expectancy [R, R, R, R]

Research shows that exercising, quitting cigarettes, and reducing inflammation can significantly improve your PON1 function and possibly increase your lifespan.

Diet

According to research, many different types of foods can increase PON1 activity. These foods primarily work as antioxidants, which stop oxidants from inhibiting PON1 [R, R].

Foods and diets that have been shown to increase PON1 expression and possibly lifespan include:

The Mediterranean Diet potentially reduces the risk of death from any cause by 7-47% [R, R]
Extra virgin olive oil has many longevity-enhancing effects, such as protecting against DNA damage, reducing the risk of heart disease, and promoting tissue regeneration [R, R, R]
Green tea, when consumed regularly, may reduce the risk of death from any cause [R, R]
Blueberries were able to extend lifespan in animal studies [R, R]
Pomegranate juice also extended lifespan in animal studies [R, R, R]
Quercetin, a polyphenol found in fruits and vegetables, increases average lifespan by up to 15% in animal studies [R, R, R]

It’s important to note that some of these findings are based on animal or cell studies. The same effect may not be seen in humans [R].

Foods rich in antioxidants extra virgin olive oil, green tea, and blueberries can increase the activity of PON1 and may potentially extend your lifespan.

Supplements

Antioxidant supplements can also increase the expression of PON1 and potentially enhance longevity. These include:

Vitamin C has been shown to increase average lifespan in animal studies [R, R]
Grape seed extract reduces the risk of heart disease and cancer, potentially giving it life-enhancing effects [R, R, R]
Curcumin increases average lifespan in animal studies [R, R]
Berberine also increases average lifespan in animal studies while also having anti-aging effects on the skin [R, R]

Once again, many of these results are based on animal or cell studies; their effects on humans is not entirely clear [R, R].

Supplements that contain antioxidants like vitamin C, curcumin, and, grape seed extract may increase PON1 activity and improve longevity.

Mathew Eng

PharmD

Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.

Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

More inflammation & autoimmunity blogs

How to Combat Histamine Intolerance Through Genetics (DAO) Are You Genetically Vulnerable to High Brain Histamine, Migraines, or ADHD? (HNMT) How to Tell if You’re Lectin Sensitive Using Your Genetic Data (CNR1) Are You Sensitive to Lectins? (MTHFR) Fight Oxidative Stress, Inflammation, and Brain Fog (PARP1) Is This Gene Causing Your Autoimmune Problems? (PTPN22) Are You Genetically Susceptible to Post-Treatment Lyme? (ABCB1) A Key Genetic Player in Autoimmunity (HLA-B) Is This Inflammation Gene Reducing Your Intelligence? (TNFSF9) Can You Manage Allergies and Asthma by Balancing Methylation? (MTHFR)

Content

What Is The PON1 Gene? How Could the PON1 Gene Boost Longevity? Your PON1 Results for Longevity

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