FOXO3A

Forkhead box O3 (or FOXO3) is a protein that acts as a transcription factor for a multitude of genes. Its activity is strongly associated with longevity via activating stress resilience, pro-longevity and anti-cancer pathways and inhibiting those with a deleterious effect upon lifespan. [R]

rs2802292

Either a T (47% chance) or a G (53% chance) allele can be present at this position. [R] Having a G results in having higher levels of FOXO3. This is to such an extent that those with G,G have a 1.50-2.75x higher chance of living to 100. [R1] [R2]

rs9400239

You have an equal chance of having a C or a T occur at this position. Having a T or two Ts enhances longevity and has also been shown to be negatively associated with waist circumference and body mass index (BMI). [R1] [R2] [R3]

SIRT1

The sirtuin enzymes (as I talked about here) are strongly associated with longevity. More sirtuin enzyme activity means more DNA repair and slower ageing. Sirtuin enzyme 1 or SIRT1 is the most studied sirtuin enzyme.

rs12778366

One can either possess a C or a T at this position. Having a C is thought to increase the production of the sirtuin enzyme SIRT1. [R] Over the course of an 18 year study, those with a C allele had a 30% lower risk of dying. [R] Those with two T alleles have an almost 9x higher risk of developing type 2 diabetes. [R]

rs3758391

Having T instead of a C at this position is associated with slowed rates of cognitive decline and improved longevity overall. [R]

CETP

Cholesterylester transfer protein (CETP) is an enzyme responsible for the transfer of cholesterol between HDL, LDL AND VLDL. Lower levels of CETP will increase HDL formation. [R]

rs118146573

Having an A allele at this position results in lower total cholesterol levels and increased risk of heart disease. [R]

RS5882

Those with a G instead of a T allele live longer and have higher HDL cholesterol, while G homozygotes (two Gs) have a 70% lower chance of getting Dementia and Alzheimer’s disease. [R1] [R2] [R3]

TP53

P53 (also known as the tumour suppressor protein) is vital in the regulation of the cell cycle and has the ability to repair damaged DNA. [R1] [R2] CRISPR gene editing technology used on P53 is being looked into as a method of preventing and/or curing cancer. [R] More than 25 different SNPs within the TP53 gene have been associated with cancer risk.

IL6

Interleukin-6 (IL-6) is a cytokine with both pro- and anti-inflammatory effects. It suppresses Th1, while inducing Th2 immune cells. [R] This means both too high levels of IL-6 and too low levels can have deleterious effects.

rs1800795

One can either have a C allele (14% chance), which results in lower IL-6, or a G allele (86% chance), higher IL-6, at this position. [R1] [R2]

A G allele increases risk of type 2 diabetes, [R] dying from acute coronary syndrome and [R] high blood pressure. [R] C alleles, on the other hand, increase risk of obesity and other metabolic diseases, [R1] [R2] Alzheimer’s disease, [R] heart attacks [R] and left ventricular hypertrophy (a risk factor for heart attacks). [R]Also, having a G allele interestingly makes someone less likely to be good at endurance but more likely to be good at sprint exercise. [R1] [R2] [R3]

Ultimately, being heterozygous (having one G and one C) at this position is ideal as it ensures IL-6 stays within a healthy range.

IGF1R

Insulin-like Growth Factor 1 has often been shown to have deleterious effects upon longevity, likely via its activation of MTOR and subsequent inhibition of autophagy and AMPK. [R] I talked about this in more detail here.

rs34516635

Having an A allele at this position may enhance longevity but also make you shorter. [R]

rs2229765

Have an A allele at this position increased longevity in men when studied by reducing IGF1 signalling. [R1] [R2]

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