Longevity and Genetics: FOXO3, CETP, IGF1, and more

Several genes have been identified as “longevity” genes. The specific variants of these genes present connections to an increased likelihood of living to be 100 or more. And…  more importantly, these particular genetic variants show links to a longer ‘healthspan’.


The term longevity refers to lifespan. People in the US, on average, live to a little over 80 years of age, but some people live to 100+ and are still relatively healthy. You may immediately assume that everyone who lives longer did everything right- exercised, meditated, ate the very best diet, etc – but that isn’t necessarily the case. In fact, researchers estimate that about 25% of the variation in lifespan is due to genetics. [ref]

What does it take to live a long, healthy life? Avoiding smoking, not drinking too much alcohol, and not getting cancer are all important for the first 80 years. Beyond that, genetics becomes really important.

What if you don’t have the longevity gene variant? Understanding the genes involved in longevity points to some ‘lifehacks’ for increasing healthy aging for everyone. For example, there are supplements, such as green tea extract, that increase FOXO3.

What are the odds of living to 100?
Someone born a hundred years ago has less than a 1% chance of being alive today. In contrast, if you are female and born in 1973 (46 years old), your odds of living to 100 are 20%. (Here is a nice chart of your odds of living to 100 based on your birth year.)

Thus, if your odds of living to 100 are 20%, carrying a genetic variant that increases that doubles the odds is fairly significant! Retirement planning is a must.

Keep in mind, though, that while genetics does play a role in how long you live, there are lots of other health and lifestyle factors that are also important. This is just about statistics here.

What needs to go on at a cellular level for healthy aging?
Cells accumulate damage and get replaced all the time, at any age. The cells in your intestines turn over fairly quickly, with a cellular turnover rate of 2-6 days. Fat cells turnover every 8 years. In contrast, most brain cells never get replaced. [ref][ref]

When cells divide, the DNA needs to be copied correctly. Yep – mitosis, you learned about it in high school biology. Errors in that DNA copy mechanism occur, and if the errors aren’t corrected, that cell may need to go through apoptosis (cell death).  DNA errors that occur in specific genes are what causes cancer…  Avoiding cancer is important for longevity.

One way to increase lifespan in animals in a lab is to decrease calories. And, shown in numerous studies with lots of different types of animals — except humans. A couple of the theoretical reasons for why calorie restriction increases lifespan include the changes to IGF1 (insulin-like growth factor 1) and autophagy.[ref] Autophagy is the cellular process of cleaning up damaged organelles and recycling cellular waste.

When it comes to the genetic variants linked to greater longevity, researchers show that genes involved in apoptosis, tumor suppression, regulating growth, and heart health are important.

Genetic variants associated with longevity:

FOXO3A gene:

The FOXO3A gene (forkhead box O3 or FOXO3) has been linked to longevity in several different studies. This gene is believed to regulate apoptosis (cell death) and function as a tumor suppressor. Also, it is involved in nutrient sensing and the response to oxidative stress.[ref][ref]

Check your genetic data for rs2802292 (23andMe v.4, v.5; AncestryDNA):

  • G/G: increased odds of living longer (1.5 to 2.75-fold increased odds) [ref][ref]
  • G/T: increased odds of living longer
  • T/T:  typical

Check your genetic data for rs1935949 (23andMe v.4, v.5; AncestryDNA):

  • A/A: increased longevity for women [ref]
  • A/G: increased longevity for women
  • G/G: typical

Check your genetic data for rs479744 (AncestryDNA only):

  • T/T: somewhat higher probability of increased longevity [ref]
  • G/T: somewhat higher probability of increased longevity
  • G/G: typical

CETP Gene:

Another gene related to longevity is the CETP gene (cholesteryl ester transfer protein) which is involved in exchanging triglycerides with cholesteryl esters.  One polymorphism that is related to longevity is rs5882 (also referred to as I405V). The G allele is associated with a somewhat longer lifespan, lower odds of dementia (including Alzheimer’s), and higher HDL levels. [ref]

Check your genetic data for rs5882 (23andMe v4, v5; AncestryDNA):

  • G/G: longer lifespan, higher HDL cholesterol, significantly decreased risk of dementia and Alzheimer’s [ref][ref]
  • A/G:  longer lifespan, higher HDL cholesterol
  • A/A:  typical

IGF1R gene:

The IGF1R gene codes for the insulin-like growth factor 1 receptor. IGF1 is a hormone that signals for growth and anabolic activities. Growth hormone levels generally fall as we age.

Check your genetic data for rs2229765 (23andMe v4, v5; AncestryDNA):

  • A/A: lower IGF levels, increased longevity [ref][ref]
  • A/G: typical longevity
  • G/G: typical

TP53 gene:

This gene codes for a protein that is important in tumor suppression.

Check your genetic data for rs1042522 (23andMe v4, v5):

  • G/G: increased longevity (possibly due to increased cancer survival) [ref]
  • C/G: slightly increased longevity
  • C/C: typical


Carrying the genes that increase my chance of living to 100 has changed my attitude and way of thinking about getting older. Planning for retirement suddenly became even more important!

Diets that increase FOXO3 and IGF1:

The Okinawan Diet is thought to promote healthy longevity, in part, through affecting FOXO3. The diet focuses on fresh vegetables, fish, lean meats, omega-3 fats, and unrefined carbohydrates.

Ketosis is theorized to decrease IGF1 and enhance FOXO3. Therefore, possibly a ketogenic diet or intermittent/periodic fasting will increase longevity. [ref][ref]

Supplements that increase FOXO3:

Green tea polyphenols (EGCG) have been found to increase FOXO3 levels. [ref]

Astaxanthin, naturally found in shrimp, salmon, and red algae, can increase FOXO3 levels. [ref] If you aren’t getting enough astaxanthin from your diet, you can get it as a supplement.

Berberine, a supplement, is often used for blood glucose regulation. Research shows that it may enhance FOXO3A. [ref]  You can get berberine as a supplement online or at your local health food store.

Related Genes and Topics:

Telomere Length: How your genes affect telomeres and aging
Telomeres are the region of repeated nucleotides (the A, G, and T’s) that are found on the ends of all of your chromosomes.  They cap off the end of the chromosomes, protecting the nuclear DNA during replication before cell division. Each time a cell divides, it makes a copy of the nuclear DNA and a little bit of the telomere is lost. When DNA replicates, it can’t replicate the very end part of the chromosome, where the telomere is located.

Klotho Gene: Anti-aging superpowers?
I’ve been fascinated by the Klotho gene for a while now, partly because it has a cool name. It is named after one of the Three Fates in Greek mythology who spin the thread of Life. Klotho (or Clotho) was responsible for the thread of life for all mortals, when they were born and when they died. As you will see, this is an aptly named gene that is intertwined with lifespan.

Originally published: Mar 2015. Revised and updated: Aug 2019.

Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.