How Might The IL-1B Gene Impact Longevity?

The IL1B gene is responsible for producing interleukin 1-beta (IL-1β), one of the major types of pro-inflammatory cytokines [R, R, R].

Cytokines are one of the main types of “messenger” molecules that the immune system uses to regulate the inflammatory response. There are many different kinds of cytokines, each with their own unique functions and roles.

When it comes to members of the interleukin-1 family (which includes IL-1β), these compounds act as a sort of “alarm” signal that are produced (by dendritic cells, macrophages, monocytes, and neutrophils) in response to cell stress, damage, or death [R, R, R, R].

These “alarm signals” then trigger the production and release of many other pro-inflammatory compounds, such as [R, R, R, R, R]:

• Reactive oxygen species (ROS), the main causes of oxidative stress
• Nitric oxide
• NF-kB
• CREB
• STAT3

IL-1β further contributes to the inflammatory response by activating Th9 and Th17 cells, as well as stimulating the production of IL-6, another major pro-inflammatory cytokine [R].

In other words, nearly all cell types in the immune system either express or are targeted by cytokines in the IL-1 family [R]. For these reasons, cytokines in the IL-1 family — such as IL-1β — are primarily associated with both acute and chronic inflammation [R, R].

The IL1B gene codes for interleukin-1-beta (IL-1β), one of the major types of cytokines that the body uses to trigger many different aspects of the inflammatory response.

Inflammation & Autoimmune Disorders

Different variants in the IL1B gene can influence how much IL-1β a person produces [R, R, R, R, R, R, R].

These differences, in turn, can influence how susceptible a person is to the effects of inflammation, and thus their likelihood of developing chronic inflammation and other associated health problems [R].

For example, SNPs in the IL1B gene have been associated with a variety of autoimmune and other inflammation-related disorders, such as:

• Rheumatoid arthritis [R, R]
• Pancreatitis (inflammation in the pancreas) [R]
• Autoinflammatory disorders, such as inflammatory bowel disease, Crohn’s disease, and ulcerative colitis [R, R]
• Severe inflammatory reactions due to common infectious diseases (such as the flu) [R]

However, the importance of IL-1β isn’t just limited to inflammatory disorders per se. This is because inflammation also contributes to the development of several other major types of health conditions, each of which can further impact lifespan.

Therefore, there are several additional major ways that genetic variations in IL1B may have an affect on overall lifespan, over and beyond the acute and chronic inflammation that IL-1β can contribute to.

Cardiovascular Health

Firstly, while acute inflammation is a normal part of the immune response, chronic inflammation can negatively impact the functioning of other organs and systems throughout the body.

One of the main systems affected by inflammation are the cardiovascular and circulatory systems. For this reason, chronic inflammation has been associated with the development of a number of significant cardiovascular health issues, including [R, R, R, R, R, R]:

• Atherosclerosis (hardening of the arteries)
• Coronary heart disease
• Myocardial infarction (commonly known as a “heart attack”)
• Heart failure
• Angina

Due to the link between elevated inflammation and long-term cardiovascular risk, certain genetic variants in the IL1B gene have been associated with the development of heart disease [R, R].

Furthermore, because cardiovascular disorders are a major cause of mortality, the link between chronic inflammation and heart disease forms another major pathway through which variants in the IL-1B gene can influence lifespan, over and beyond the “direct” effects of inflammation by itself.

Cancer Risk

Secondly, the other major way that IL1B may impact lifespan is by influencing a person’s long-term risk of developing cancer.

This is because — similar to cardiovascular health — evidence suggests that increased inflammation may be one potential causal factor in the development and growth of tumorous cells [R, R, R].

Although the link between inflammation and cancer is a general one, cytokines in the IL-1 family in particular have been associated with the early stages of cancer development and tumor growth. By extension, variants in the IL1B gene that increase the expression of IL-1β could increase a person’s long-term risk of developing cancer — which would have obvious negative effects on their likelihood of living long into older age [R].

The effects of IL1B on lifespan are due to its association with chronic inflammation. While this effect is already significant on its own, inflammation can also contribute to the development of autoimmune disorders, cardiovascular issues, and cancer — all of which can further impact a person’s overall lifespan.

You can see your genotypes for several different IL1B SNPs in the table below. However, keep in mind that these results are based purely on association studies, and much more research will be needed to know what role — if any — these variants play in actually directly impacting a person’s overall lifespan.

By extension, just because a person might have some “risk-associated” genotypes for some of these SNPs does not necessarily mean that they will actually develop the health condition associated with it!

This is because there are many different genetic, lifestyle, and environmental factors that can affect overall health and lifespan. In other words, just having a few “bad” IL1B genotypes does not necessarily predict anything specific about a person’s lifespan — rather, these results illustrate just one of the many different genetic factors potentially related to it.

With that in mind, the following table summarizes your results for several different IL-1B SNPs that have been potentially linked to longevity:

“Main” IL1B SNP (rs16944):

One of the more highly-studied SNPs in the IL1B gene is rs16944, also often referred to as the ‘C-511/T’ polymorphism. When it comes to this SNP, it is probably best to have the ‘GG’ (homozygous minor genotype), which about 25% of the general world population carries.

However, this genotype is also significantly more common in certain ethnic populations. For example, up to 40-45% of people of European descent have this genotype. Therefore, the relative chances of you having this genotype may depend on your unique ancestral background.

According to multiple targeted gene studies in many different ethnic populations, the (non-beneficial) ‘A’ allele of rs16944 has been associated with:

• Rheumatoid arthritis [R]
• Acute pancreatitis (inflammation in the pancreas) [R]
• Increased rates of various types of cancer (including cervical, prostate, gastric, bone marrow, and breast cancers) [R, R, R, R, R, R, R]
• Increased risk of mortality from systemic infections, such as septic shock [R]
• Increased risk of severe reactions to common infectious illnesses, such as the flu [R]
• Reduced rates of survival among elderly patients admitted to geriatric hospital care (males only) [R]

Although the mechanisms of this SNP have not yet been directly confirmed, it is highly likely that these associations are due to elevated levels of IL-1β, for two main reasons:

1. Firstly, this SNP is located in the “promoter” region of the IL1B gene, which is the section of a gene that generally plays the most direct role in determining how much a gene actually gets expressed throughout the body. Therefore, variants in these SNPs are likely to play a relatively direct role in controlling how much IL-1β the body produces [R, R].
2. Secondly, many targeted gene studies of IL-1B have measured the actual levels of IL-1β in people with different genotypes — and these studies have consistently reported that carrying more ‘A’ alleles for this SNP is typically correlated with higher levels of IL-1β circulating throughout the body [R, R, R, R].

Therefore, the effects of this SNP on longevity are highly likely being driven by increased levels of IL-1β, which in turn may raise a person’s susceptibility to chronic inflammation (and its secondary effects on other organ systems) [R].

Other Noteworthy IL1B SNPs:

IL1B rs1143623:

• Also known as the ‘-1464 C/G’ polymorphism
• SNP located in “promoter” region of IL1B gene [R]
• The ‘C’ allele has been associated with rheumatoid arthritis [R] and breast cancer (in Han Chinese) [R]
• ‘C’ alleles also directly linked to increased (serum) levels of IL-1β [R, R]

IL1B rs1143627:

• Also known as the ‘IL-1B-31’ polymorphism
• The ‘AA’ genotype (homozygous minor) has been associated with increased rates of several types of cancer [R, R, R, R]
• The ‘AA’ genotype has also been directly linked with increased IL1B gene expression (IL-1B mRNA levels) [R]

IL1B rs1143634:

• The ‘A’ allele for this SNP has been associated with increased rates of acute pancreatitis (inflammation in the pancreas) [R]

IL1B rs3136558:

• The ‘G’ allele for this SNP has been associated with reduced rates of cervical cancer [R]

IL1B rs1143630:

• The ‘T’ allele of this SNP has also been associated with reduced rates of cervical cancer [R]

As you can see from the lists above, the negative health outcomes that have been associated with these IL1B gene variants are quite diverse, and cover many of the different potential health conditions associated with chronic inflammation (such as autoimmune disorders, cancer development, etc.). This illustrates the many potential specific pathways that may link certain IL1B variants with differences in overall lifespan.

Several SNPs in the IL1B gene have been associated with the long-term development of a variety of health conditions that can impact lifespan, such as chronic inflammation, autoimmune disorders, and cancer risk.