Analyzing DNA to Determine a Person’s Age

Birthday cakePeople have employed many methods to disguise their age: eating a healthy diet rich in antioxidants, exercising regularly, protecting their skin from the sun and, if all else fails, undergoing plastic surgery. However, a recent Current Biology paper may make it harder for us to hide our true age. The authors describe a real-time PCR assay that can provide an estimate of a person’s age based on a tiny blood sample (1).

“How does that work?” you might ask. Well, the assay is quite ingenious and relies on the rearrangement of T cell receptor (TCR) genes. For those you who, like me, need a quick refresher in immunology for this all to make sense, join me for a brief lesson about TCR gene rearrangements: T cells, also known as T lymphocytes, are one of our body’s immunological defense systems against foreign invaders such as bacteria, viruses and parasites, as well as tumor cells. A T cell’s ability to recognize these nasties is mediated by the T cell receptor, a hetermodimer composed of alpha and beta subunits. To recognize a multitude of foreign antigens, T cells must express a broad repertoire of T cell receptors, but that diversity is not encoded by an army of TCR genes. Instead, diversity arises through DNA rearrangement of genes that encode the TCR alpha and beta subunits (as well as random addition of nucleotides during DNA rearrangement). The TCR beta gene is composed of multiple variable, diverse and joining segments (V, D and J, respectively), while the TCR alpha gene is composed of V and J segments. As T cells differentiate in the thymus, VDJ recombinases recognize recombination signal sequences flanking the V, D and J segments in the TCR beta gene and catalyze the joining of a D segment to a J segment, then the joining of one V segment to the DJ sequence. The TCR alpha gene undergoes similar DNA rearrangements. During recombination, the intervening DNA sequence forms a hairpin loop and is cleaved to form a small circular DNA fragment called a TCR excision circle (TREC). The resulting TREC is exported from the thymus and can be detected in the bloodstream.

TREC levels in the blood are an indicator of thymic function (2) and, because thymus function begins a life-long decline shortly after birth, age. Zubakov et al. use real-time PCR to quantify one particular TREC, δRec-ψJα sjTREC, in 195 Dutch individuals ranging in age from several weeks to 80 years. Through normalization with the single-copy albumin gene and linear regression analysis, the authors of this paper were able to correlate age with TREC levels in the blood. The standard deviation of their assay is ±8.9 years, which might seem rather high, but the accuracy and precision are better than those of other genetic methods to determine age, such as the accumulation of mitochondrial DNA deletions or telomere shortening (3). Furthermore, the authors found no statistical difference in age estimates from fresh blood samples and blood samples that had been stored for 1.5 years, making this assay amenable to the analysis of archived blood samples.

One obvious use of this new assay is in forensic science, where using DNA to predict physical traits is an emerging field of research called forensic phenotyping. Forensic scientists are developing genetic assays to provide insight into a person’s appearance, such as eye, hair or skin color, to help identify the perpetrator of a crime. Scientists can now add a person’s age to the list of phenotypic characteristics that can be determined through DNA analysis.

The fact that the results could be off by as much as 8.9 years in either direction makes me think that this TREC assay is more of a solid first step in developing more advanced genetic assays to determine age. I think assay precision will need to be much higher for the results to be informative in most criminal investigations, considering that the majority of criminals fall within a certain, relatively narrow age range. Plus, it is still unknown what effect immunological diseases, such as HIV/AIDS or leukemia, or a person’s ancestry or environment has on TREC levels and, therefore, assay results. Additional research is needed before the assay can be applied in the real world. The assay has potential though, especially because the assay requires as little as 50ng of human DNA (or as little as 5ng in young people) and because blood is a relatively common sample recovered from a crime scene, unlike teeth or skeletal elements, which are required for odontological or skeletal approaches to age determination.

So, for the time being at least, anyone who hesitates to reveal his or her true age can continue to dodge the question or subtract a few years from his or her true age with no real danger that DNA will reveal the truth.

References
1. Zubakov, D., Liu, F., van Zelm, M.C., Vermeulen, J., Oostra, B.A., van Duijn, C.M., Driessen, G.J., van Dongen, J.J., Kayser, M. and Langerak, A.W. (2010). Estimating human age from T-cell DNA rearrangements. Current Biology: 20, R970–1. PMID: 21093786.
2. Geenen, V. et al. (2003) Quantification of T cell receptor rearrangement excision circles to estimate thymic function: An important new tool for endocrine-immune physiology. J. Endocrinol. 176, 305–11.
3. Meissner, C. and Ritz-Timme, S. (2010) Molecular pathology and age estimation. Forensic Sci Int. 203, 34–43.

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Terri Sundquist

Terri has worked as a Scientific Communications Specialist at Promega Corporation for more than 13 years, and prior to that, spent more than 5 years solving problems and answering questions as a Promega Technical Services Scientist. She graduated with B.S. degrees in Chemistry and Biology at the University of Wisconsin—River Falls, then earned her M.S. in Molecular Biology from the Mayo Graduate School in Rochester Minnesota.

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