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Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.
Aging is an incredibly complex phenomenon. It’s driven by a mix of genetic factors, the gradual buildup of wear-and-tear in our cells, and everyday choices about diet, exercise, and how we handle stress. More important than simply living longer is making sure those added years are fulfilling and vibrant. That’s why researchers and health professionals are focusing on “healthspan,” the length of time we stay healthy, rather than just the total number of years we’re alive.
By digging into the biology of aging, supporting public health initiatives, and encouraging personal lifestyle changes, we can potentially delay many of the health issues that come with getting older. The payoff? A better chance at remaining active, independent, and enjoying life well into our later years.
Would you like to understand your age-related genes in more depth? Check out LifeDNA’s Aging Report.
BPIFB4 (short for BPI fold-containing family B member 4) is a human gene that encodes a protein belonging to a group known as the BPI fold-containing family. The “BPI fold-–containing family” is a group of proteins that share a specific three-dimensional shape known as the BPI fold.
The letters “BPI” stand for “bactericidal/permeability-increasing,” referring to proteins that can bind and neutralize bacterial components, helping the immune system fight infections. Since the family of proteins that have this structural fold tend to share functional similarities in immune response and inflammation control, they are grouped under this umbrella term.
The Longevity-Associated Variant (LAV-BPIFB4) is a specific version of the BPIFB4 gene that has been linked to healthier aging and a longer lifespan. Researchers found this variant more often in people who live to very old ages, such as centenarians. It appears to have protective effects on the body, especially in maintaining cardiovascular health and reducing inflammation.
Several aspects of aging and longevity are tied to LAV-BPIFB4:
An aging heart gradually loses function, and current treatments cannot fully prevent this decline. Some individuals maintain heart health into old age due to beneficial genetic factors, including the LAV of BPIFB4.
A 2023 study showed that LAV-BPIFB4 carriers experience fewer cardiovascular issues. Delivering this gene via gene therapy improves heart function in disease models. In elderly patients with heart failure, pericytes (cells supporting blood vessels) are significantly reduced. However, this defect was less severe in those with the LAV-BPIFB4 genotype. Supplementing with LAV-BPIFB4 restored pericyte function, improved blood vessel support, and prevented heart deterioration in mice. These findings suggest that LAV-BPIFB4 could be a promising therapy to slow or reverse heart aging.
A 2021 study showed that LAV-BPIFB4 plays a crucial role in protecting the heart by supporting key enzymes like eNOS and PKC-alpha.
LAV-BPIFB4 therapy also restores immune balance by lowering inflammation and enhancing protective factors, mimicking the natural advantages seen in long-lived individuals. These findings suggest that LAV-BPIFB4 could be an important target for treating cardiovascular diseases and promoting healthy aging.
Understand the Genetics of Vascular Aging in more depth
Inflammation plays a crucial role in longevity because chronic low-grade inflammation, often called “inflammaging,” is a key driver of aging and many age-related diseases. While short-term inflammation helps the body fight infections and heal injuries, persistent inflammation over time can damage tissues, accelerate cellular aging, and increase the risk of conditions such ascardiovascular disease, diabetes, neurodegeneration, and cancer.
Read our deep dive analysis of the “Genetics of Inflammatory Response”
Long-lived individuals, such as centenarians, tend to have better-regulated immune responses with lower levels of chronic inflammation and higher levels of anti-inflammatory factors. According to a 2023 study, centenarians exhibit a unique immune profile characterized by higher levels of both pro-inflammatory and certain regulatory cytokines compared to middle-aged individuals. While markers of inflammation such as TNF-α, IL-6, IFN-α, and IL-23 were elevated, the study also found an increase in IL-19, a cytokine that shifts immune responses toward a less inflammatory state.
The immune systems of centenarians remain more balanced, allowing them to fight infections effectively without excessive inflammatory damage. Research suggests that gene variants linked to longevity, such as LAV-BPIFB4, may help control inflammation by modulating immune system activity and reducing harmful inflammatory markers.
Lifestyle factors also play a major role in controlling inflammation. A healthy diet (rich in antioxidants and healthy fats), regular exercise, stress management, and good sleep habits can all help keep inflammation in check, supporting longer and healthier lives.
Ultimately, reducing chronic inflammation is a key strategy for improving healthspan, the number of years a person remains healthy and functional.
In an article published in 2024, researchers used a high-throughput proteomic approach to analyze circulating proteins in 591 participants from the PLIC cohort based on their BPIFB4 genotype. The study found that individuals with homozygous LAV-BPIFB4 had lower levels of immune-inflammatory markers compared to those with other BPIFB4 variants. Further in vitro experiments on intestinal epithelial tissues from inflammatory bowel disease (IBD) patients showed that LAV-BPIFB4 treatment had beneficial effects, suggesting its potential role in improving intestinal health and immune regulation.
Scientists are still exploring ways to use LAV-BPIFB4 in medicine, including using it via gene therapy and small molecules that could mimic its effects. While the research is still in the early stages, this variant could one day help people stay healthier for a longer time.
The BPIFB4 gene, particularly its Longevity-Associated Variant (LAV-BPIFB4), is linked to healthier aging by supporting heart function, reducing inflammation, and improving immune balance. Found more often in centenarians, this variant enhances vascular health by boosting nitric oxide production and protecting blood vessels. Research shows it may help prevent age-related diseases and has potential for gene therapy. Studies have also found that those with LAV-BPIFB4, with lab tests suggesting benefits for intestinal health. While still in the early stages, LAV-BPIFB4 could be key to extending healthspan and delaying aging-related decline.
