inflammation & autoimmunity

longevity

TNF

Can This Inflammation Gene Affect Lifespan? (TNF)

Written by Mathew Eng, PharmD on January 25th, 2020

The TNF gene plays a key role in the body’s inflammatory and immune response. Research suggests that certain genetic variations of TNF may be linked to longer lifespans. Find out what this gene does and how it can affect longevity.

What Is The TNF Gene?

The TNF gene plays an important role in the body’s immune response and inflammation. It does this by coding for a protein called tumor necrosis factor alpha (also known as TNF-alpha or cachexin) [R].

TNF-alpha is a type of cell signaling protein known as a cytokine. It is produced by several different components of the immune system, including [R]:

Macrophages
Natural killer (NK) cells
Neutrophils
Mast cells

Genetic variations in the TNF gene may cause improper production of TNF-alpha, which has been associated with a number of health conditions, such as autoimmune disease, depression, and cancer [R, R, R].

How Does TNF-alpha Work?

As mentioned, the TNF gene codes for the TNF-alpha protein, which belongs to a class of compounds called cytokines.

TNF-alpha is primarily responsible for regulating cells in the immune system. It has several functions throughout the body, many of which are in combination with IL-1 and IL-6 [R].

Some of the effects of TNF-alpha include [R]:

Inflammation and fever
Appetite suppression
Stimulating phagocytosis, which helps remove harmful substances like bacteria

TNF and Longevity

Supporting Evidence

There is some evidence that certain genetic variants in the TNF gene may be associated with longevity. More specifically, a variation in the SNP rs1800629 (sometimes called TNF -308) may be more common in those that live exceptionally long lives.

For example, one study looked at 1,196 people from a population of Tatars, an ethnic group that resides in several countries, including Russia, Ukraine, and Uzbekistan [R].

In the study, researchers found that the ‘GG’ genotype was more common in those that live over 90 years, but only in Tatar women. This association does not appear to affect men [R].

Another study also looked at rs1800629 in 1,057 Caucasian patients who were hospitalized for critical illness [R].

The researchers of this study suggest that the ‘GG’ genotype is significantly more common in patients who survive critical illness. The ‘AA’ genotype was associated with higher rates of death and time spent on a ventilator [R].

The ‘GG’ genotype may be more common in those that live very long lives, at least in female Tatar populations. It may also be associated with better survival during critical illness.

Conflicting Evidence

Not all studies have found a link between the TNF gene and longevity.

For example, one study of 650 Finnish people found no association between rs1800629 and longer lifespans [R].

On top of that, a meta-analysis of 4 studies of rs1800629, which included a total of 5,937 Caucasian people, concluded that this SNP does not affect the probability of reaching an advanced age [R].

Research also suggests there may be no association between TNF and longevity in Jordanian and Uyghur populations [R, R].

How Does TNF Affect Lifespan?

Research shows that the ‘AA’ genotype in TNF rs1800629 may lead to increased production of TNF-alpha in the body [R].

This increase in TNF-alpha levels may lead to imbalances in the body’s immune and inflammatory response, which may potentially increase the risk of death [R, R].

In addition, the ‘AA’ genotype may be associated with a number of health disorders, including:

Asthma and COPD [R, R]
Heart disease [R]
Rheumatoid arthritis [R, R]
Systemic lupus erythematosus (SLE) [R]
Cancer [R, R]

Your TNF Results for Longevity

You can see your genotypes for TNF in the table below. However, keep in mind that these associations are based on studies from certain ethnic populations — so you should interpret your results with caution if you are not descended from one of these specific groups!

SNP Table

variant	genotype	frequency	risk allele
rs1800629

Primary SNP:

TNF rs1800629

‘A’ = No association with longevity
‘G’ = More common in those with longer lifespans in certain populations
About 82% of people have the ‘GG’ genotype
The association between the ‘GG’ genotype and longevity has only been found in certain Tatar groups

Recommendations

Lifestyle

Exercise Regularly

Exercise can be a great way to reduce inflammatory factors (such as TNF-alpha) and ultimately improve longevity [R, R].

Although TNF-alpha levels can actually increase immediately after exercise (especially after vigorous physical activity), regular exercise decreases inflammation in the long run [R, R, R, R].

Research shows that exercise is particularly effective for reducing age-related inflammation in the elderly [R, R].

But regardless of the relationship between exercise and TNF-alpha, research consistently shows that regular physical activity is one of the best ways to extend lifespan and quality of life [R, R, R].

On the other hand, a sedentary lifestyle is strongly associated with a significantly higher risk of death [R, R].

How much should you exercise? Most organizations, including the American Heart Association, recommend getting at least 150 minutes of moderate aerobic exercise each week [R].

Weight Management

Research shows that TNF-alpha levels are directly linked to weight. More specifically, blood levels of TNF-alpha appear to increase as abdominal fat increases [R, R].

This is because fat (adipose) tissue may stimulate the expression and production of TNF-alpha. Reducing weight may lead to lower levels of TNF-alpha and inflammation [R, R].

In any case, there is strong clinical evidence that obesity is a risk factor for a number of health disorders and is associated with shorter lifespan. Managing your weight to a normal BMI is an effective way to improve longevity [R, R].

Quit Smoking

Clinical studies demonstrate that tobacco smokers have significantly higher TNF-alpha levels in the blood compared to nonsmokers [R, R].

Inhaled cigarette smoke can increase the production of TNF-alpha in lung cells, which can lead to airway inflammation and lung damage [R, R].

Besides its effects on TNF-alpha, smoking is one of the leading causes of preventable death. For smokers, quitting can significantly improve life expectancy [R].

Diet

There is evidence that diet plays a key role in TNF-alpha levels, inflammation, and longevity.

Animal studies show that diets high in fat and carbohydrates can increase the expression of TNF-alpha [R, R].

Based on clinical trials, there are some specific foods that may decrease inflammatory markers, such as TNF-alpha. These foods include:

Fruits and vegetables [R]
Olive oil [R]

In addition, several studies show that a Mediterranean diet (which includes the above mentioned foods) also reduces TNF-alpha and is associated with lower inflammation [R, R].

There is also clinical evidence that the Mediterranean diet itself is associated with improved longevity [R, R].

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)

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