Genetics & Longevity Variants

The ACE insertion/deletion (I/D) polymorphism (rs4646994) is a 287-base-pair stretch of DNA (an Alu repeat). It is either present or absent in intron 16 of the ACE gene. The D…

The APOE ε4 allele is a gene variant that makes the E4 form of apolipoprotein E. It differs from the common ε3 form by a single building block at position 112 (cysteine swapped…

ATM (short for ataxia-telangiectasia mutated) is a gene that makes a protein kinase. That kinase is the master alarm for one of the worst kinds of DNA damage: a double-strand…

CETP (cholesteryl ester transfer protein) swaps cholesteryl esters out of HDL for triglycerides from VLDL and LDL, which effectively lowers your HDL cholesterol. The I405V…

DNA repair pathways are the conserved systems your cells use to find and fix genetic damage. The load is huge. Internal sources alone cause up to 100,000 lesions per cell per…

An epigenome-wide association study (EWAS) is a hypothesis-free scan. It tests whether DNA methylation at hundreds of thousands of CpG sites (spots where a cytosine next to a…

FOXO3 is a gene for a transcription factor. It sits at a crossroads of longevity pathways. It integrates signals from the insulin/IGF-1 and AMPK pathways. With those, it controls…

A genome-wide association study (GWAS) is a hypothesis-free scan of the common variants in your DNA (SNPs, usually present in over 1 to 5% of people) across the whole genome. It…

The KL-VS haplotype of the klotho gene is a set of six linked variants. Two of them change amino acids (F352V and C370S) in exon 2. It raises serum klotho protein. And it is tied…

LMNA is a gene that makes two nuclear-skeleton proteins, Lamin A and Lamin C (via alternative splicing). These lamins form a mesh just under the inner nuclear membrane of your…

Mitochondrial haplogroups are family branches of your mitochondrial DNA (mtDNA), which you inherit only from your mother. Each branch is defined by a shared set of DNA tweaks,…

mtDNA heteroplasmy is when a single cell, tissue, or person carries two or more different mitochondrial DNA sequences. It is a mix of normal (wild-type) and mutant copies. The…

The MTHFR C677T variant (rs1801133) is a common tweak in the MTHFR gene that makes a heat-sensitive, slower version of the enzyme. People with two copies (TT) keep only about 30%…

PCSK9 is both a gene and a hot drug target for lowering cholesterol. The protein (a serine protease made by your liver) latches onto the LDL receptor and sends it to be destroyed…

Pharmacogenomics is the study of how your genes change the way you respond to drugs, both how well they work and how toxic they are. The genes that matter most code for…

A polygenic risk score (PRS) sums up your genetic risk for a trait across many small DNA variants (SNPs). Each variant gets a weight, usually drawn from big genome-wide studies…

A single-nucleotide polymorphism (SNP, said 'snip') is a germline variation at a single base-pair position. It exists where two or more nucleotide alleles occur in the population…

Sirtuins are a family of enzymes that depend on NAD⁺ to remove chemical tags from proteins. The three most studied for longevity differ sharply in where they work and what they…

Somatic mutations are DNA changes that arise in your body cells after conception, not in the germline. They affect only the descendants of the cell where they happen. Every cell…

TERT and TERC are the two core parts of telomerase. Telomerase is the enzyme that rebuilds the protective caps (telomeres) on your chromosomes. TERT (telomerase reverse…

Whole-genome sequencing (WGS) reads every letter of your DNA, in both the nuclear genome and the mitochondria. Older SNP chips miss a lot. WGS can spot rare changes:…

WRN is a gene that makes a DNA-repair enzyme, part of the RecQ helicase family. It has both helicase and exonuclease activities. It works in several repair pathways: base…