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Can Aging Be Stopped?

September 29, 2017

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Many people are shocked when they find out that the concept of aging can be explained by genetics through telomeres. Telomeres are 8000-10000 nucleotide protective caps on the ends of strands of DNA. They protect the genome from degradation, repair and unnecessary recombination. In normal cellular processes, telomeres shorten with each cell division, but when the length reaches a critical limit, the cell stops dividing and most likely dies. Therefore, many scientists think that telomere length acts as an “internal clock” to determine the lifespan of a cell and organism.

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Does this mean that if you prevent shortening of telomeres, cells won’t die?

In fact, research shows that this is what allows cancer cells to continuously divide and survive. Cancer cells contain human telomerase genes that code for an enzyme called telomerase. Telomerase regulates telomere length. This is a function that normal, non-cancerous cells lack.

Telomere research has been increasing in the past few years, along with research about cancer and aging. People are finding that the life span of cells can be increased experimentally by increasing telomere lengths, but are also connecting lifestyle choices with telomere lengths.

Scientists at the Stanford University School of Medicine have found a way to lengthen telomeres by as much as 1,000 nucleotides by using modified messenger RNA, that contains a coding sequence for the active component of telomerase. The scientists found that cells with lengthened telomeres were able to divide up to 40 times more than untreated cells. A professor of microbiology and immunology even said that this is a way to “[turn] back the internal clock in these cells by the equivalent of many years of human life.”

Outside of these methods to increase telomere length, research has also been done in how lifestyles with obesity, smoking, and stress affect telomere shortening. A researcher, Masood, has shown that obesity is associated with oxidative stress, due to the deregulated production of products by adipose tissue, that can further induce DNA damage and expedite telomere shortening. Another study in the medical journal Preventive Medicine, finds that people who have high levels of physical activity have significantly longer telomeres than those with sedentary lifestyles. Although the exact mechanism of this is unknown, it is predicted to also be tied with inflammation and oxidative stress over time.

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Research in this area is ongoing, and it is believed that telomeres will provide significant breakthroughs in the areas of cancer treatments but also preventing aging.

References:

Shammas, Masood A. “Telomeres, Lifestyle, Cancer, and Aging.” Current Opinion in Clinical Nutrition and Metabolic Care 14.1 (2011): 28–34. PMC. Web. 26 Sept. 2017.

Jafri, Mohammad A. et al. “Roles of Telomeres and Telomerase in Cancer, and Advances in Telomerase-Targeted Therapies.” Genome Medicine 8 (2016): 69. PMC. Web. 26 Sept. 2017.

Brigham Young University. “High levels of exercise linked to nine years of less aging at the cellular level: New research shows a major advantage for those who are highly active.” ScienceDaily. ScienceDaily, 10 May 2017. <www.sciencedaily.com/releases/2017/05/170510115211.htm>.

https://med.stanford.edu/news/all-news/2015/01/telomere-extension-turns-back-aging-clock-in-cultured-cells.html

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  Timothy Durham was convicted of rape when a test showed his DNA genotype matched the DNA recovered from the crime scene. Eye witnesses testified that Durham was in a different state at the time of the incident, but he wasn’t exonerated from his 3000 year sentence until follow up DNA analysis showed that the preliminary forensic analysis used in the trial was misinterpreted (Thomas et al.). DNA testing serves an invaluable part in our criminal justice system, but it comes with complications and bias that can lead to wrongful convictions and misinformed juries.  

Background:

Forensic genetics aims to identify the origin of a biological sample. It can be traced back to Karl Landsteiner who discovered human ABO blood groups. With blood groups, suspects could be eliminated based on their blood type. For example, if a suspect had type A blood and there was type B blood left at the scene by the perpetrator, the investigators could rule out the suspect. Unfortunately, the reverse didn’t work. If the suspect and perpetrator both had the same blood type, it can’t be concluded that the suspect was guilty. Blood identifiers evolved into 8 distinct categories which improved the ability to eliminate suspects, but could only conclude that (if the system matched) it might be the perpetrator or this person might be related to the perpetrator (Jobling and Gill). The field evolved in the 1980s with the discovery of Minisatellites, lines of repetitive DNA that don’t encode proteins. Minisatellite patterns in DNA create what we know today as the DNA fingerprint, and it has a much higher accuracy rate than previous methods (Augustyn et al.). Around the same time, a breakthrough for victims of sexual assault was discovered. In the case of assault, bodily fluids of both the victim and the assaulter can get mixed. A process called differential lysis was created which could selectively increase the concentration of sperm in a fluid sample thereby allowing for accurate DNA testing (Jobling and Gill). Forensics evolved to use single-locus probe testing after several years because of its ease of interpretation. It looked at specific minisatellites that had high variability between subjects. This was the first DNA-based method to be used in a criminal investigation. Two murder homicides from several years apart were connected using DNA evidence. The evidence was then used to exonerate an innocent man, and the guilty party was found when he tried to evade mandatory DNA testing for all men in the small town. His guilt was then reinforced when the DNA profiles matched, and he gave a confession (Jobling and Gill). Finding DNA at a crime scene doesn’t guarantee that you’ll find a murderer. There are issues with non-pure samples and limited samples that make DNA work difficult, and accreditation of facilities and new techniques and take time (Jobling and Gill).  

Subjectivity of DNA Interpretation:

In a 2009 publication, the National Academy of Science discusses the possibility for subjective influence in lab based forensics. The interpretation bias happens in complex cases where, for example, there could be a mixture of DNA. A study published in 2011 looked specifically at this issue. A gang rape happened in Georgia, and the mixture in DNA from the case was used to prosecute one suspect after another suspect took a plea bargain to testify against him. With DNA mixtures, there are three possible conclusions: suspect excluded, suspect cannot be excluded, and inconclusive. If the suspect is excluded, it means that there’s little to no possibility that his DNA is part of the sample. If the suspect cannot be excluded, it means that there’s a possibility that his DNA is part of the sample. In the trial, the DNA examiners who knew the context of the case concluded that the suspect being prosecuted could not be excluded. The 2011 study gave the DNA evidence from this case and the DNA profiles of the suspects to 17 forensic examiners. These examiners had no context of the case, and they all worked independently. Of the 17, only 1 came to the same conclusion (suspect cannot be excluded) as the examiners who knew the context of the case. Twelve of the 17 concluded that the suspect who was prosecuted and convicted had no relation to the DNA found in the sample. Not only does this show that subjectivity occurs due to the context of the case, but the 17 examiners came up with different findings based on their past experiences meaning that not all DNA analysis is objective. Some organizations like the Scientific Working Group on DNA Analysis Methods say that quantitative statistical evidence should be presented with every categorical conclusion, but the US doesn’t require this (Dror and Hampikian).

False Positives:

There are two categories that cause wrongful identification in a DNA report: coincidental matches and false positives. Coincidental matches are DNA matches between two unrelated people. The probability of these matches is about 1 to 500,000 for white individuals and about 1 to 350,000 for black individuals. This small probability of coincidental matches makes people feel confident in DNA evidence. False positives, on the other hand, are matches between DNA and test DNA that result from issues in the forensics lab. There have been multiple cases of forensics labs accidentally switching victim and suspected rapist DNA which lead to convictions that were later overturned when the lab realized the error. There are also cases of misreading or misunderstanding a sample. In a case from 1993, a man was convicted of rape because someone interpreted a mixed sample of victim and perpetrator DNA as an individual sample. The conviction was again overturned. To prevent false convictions, retesting DNA is allowed, but it’s not an efficient solution. Many people are pushing for statistical information on the probability of false positives, so that the jurors can make accurate judgements based on DNA evidence (Thomas et al.).  

Conclusion:

DNA analysis is a useful tool for the criminal justice system, but subjectivity can be an issue in forensic testing. To combat wrongful convictions, there are organizations like The Innocence Project who use DNA testing to free the innocent, but reformed forensic testing standards should be put in place to prevent subjectivity and to ensure juries are correctly informed during trials. https://www.innocenceproject.org/    

Citation:

Augustyn , Adam, et al. “DNA Finerprinting.” Encyclopedia Britannica , 26 Apr. 2018, www.britannica.com/science/DNA-fingerprinting#ref153186. Dror, Itiel E., and Greg Hampikian. “Subjectivity and Bias in Forensic DNA Mixture Interpretation.” Science & Justice, vol. 51, no. 4, 2011, pp. 204–208., doi:10.1016/j.scijus.2011.08.004. Jobling, Mark A., and Peter Gill. “Encoded Evidence: DNA in Forensic Analysis.” Nature Reviews: Genetics, vol. 5, no. 10, Oct. 2004, pp. 739–751., doi:10.1038/nrg1455. Thompson, William C, et al. “How the Probability of a False Positive Affects the Value of DNA Evidence.” Journal of Forensic Sciences, vol. 48, no. 1, Jan. 2003, pp. 1–8., doi:10.1520/jfs2001171.