This isn’t some sort of Jedi mind trick, we promise, but TERT may not be the anti-aging target you are looking for! TERT, or telomerase reverse transcriptase, plays an essential role in the elongation and maintenance of telomeres and as telomeres shorten with age, many surmise that activation of TERT represents an exciting approach to stave off the signs of aging.
However, a recent study from a multidisciplinary team of padawans and apprentices led by the Jedi Masters Ken K. Ong, Kenneth Raj, Kathryn L. Lunetta, and Steve Horvath has now established that longer telomeres do not correlate to younger biological age as measured by the DNA methylation level of select CpGs on the 450K array, a measure known as the epigenetic clock. Of note, individuals exhibiting an epigenetic age older than their chronological age display a higher risk of all-cause mortality, while the children of parents who reach over 100 years of age generally exhibit a younger epigenetic age.
Here are the details of this fascinating new study:
- The authors undertook a genome wide association study (GWAS) of white blood cells from around 10,000 individuals to discover genetic variants associated with accelerated epigenetic aging
- 5 loci correlated to intrinsic epigenetic age acceleration (IEAA), a measure based on 353 CpGs that is independent of age-related changes in blood cell composition
- 3 loci correlated to extrinsic epigenetic age acceleration (EEAA), a measure based on 71 CpGs that takes the contribution of blood cell composition into consideration
- Interestingly, one loci associated with IEAA mapped to the TERT gene
- This finding associates accelerated epigenetic aging with telomere elongation/longer telomeres, an unexpected outcome
- In vitro analysis confirmed that TERT expression in human primary fibroblast cells leads to increased epigenetic aging, which studies have linked to multiple detrimental signs of aging
- Mendelian randomization analyses also revealed that age of onset of first menstruation (menarche) and menopause have causal effects on IEAA
Co-author Douglas P. Kiel provides some more thoughts, “TERT is a subunit of the enzyme telomerase, which is a widely known enzyme because it has been touted as an anti-aging enzyme. It has been called a modern fountain of youth. However, some scientists have pointed out that it is unlikely to become a source of anti-aging therapies. Our study highlights the error in the notion that activation of telomerase (as advocated by some) will cure aging. Instead, our study shows that an anti-aging therapy based on telomerase expression would be accompanied by continued aging.”
For a more in-depth look for the data you are most definitely looking for, take your speeder over to Nature Communications, January 2018.