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The Impact of Genetic Innovations on Longevity

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The 20th century witnessed steady and dramatic extensions of longevity in the United States. At the beginning of the 20th century, U.S. life expectancy was just under 50 years. By the end of the century, it had extended to almost 80 years.

This advance was the result of three fairly discrete developments:

  • The first part of the 20th century benefitted from basic public health improvements, such as refrigeration, indoor plumbing and sewage-treatment programs, which significantly reduced mortality from infectious diseases.

  • The middle of the century saw further reductions in infectious diseases-this time due to widespread use of antibiotics and vaccines.

  • The latter part of the century benefitted from a halving of cardiovascular mortality, which was the result of new surgical procedures, such as bypass surgery; better diagnostics, such as sound-wave imaging; risk-mitigating drugs, such as statins for cholesterol and the anti-hypertensive medications; and lifestyle changes, most notably the decline in smoking.

Now that we are into the first decade of the 21st century, the question is whether or not we can expect a continuation of the longevity improvements of the 20th century. From a simple mathematical perspective, our odds would appear to be lower. Despite the improvements in longevity in the 20th century, our biological age has not changed. Virtually no one lived beyond age 120 at the beginning of the 20th century, and virtually no one does so today. We have increased the percentage of people getting close to our biological limit and, in the process, we have extended average life expectancy. But we must question whether we can expect the same degree of improvement in longevity, when we now are starting with a life expectancy that is two-thirds of our biological limit, as contrasted with one that was only five-twelfths of our limit at the beginning of the 20th century-that is, unless we can extend our ultimate biological limit.

In that regard, one of the most interesting questions facing us has to do with the possible impact of genetic innovations.

Results of human twin studies suggest that only about 20% to 30% of the variation in surviving to an age of 85 is determined by genetics. A recent study on the genomes of people living to at least 100 years of age published by a group of researchers at Boston University demonstrated that a variety of genetic signatures were predictive of longevity. These “longevity associated variants” (LAVs) were associated with significant delays in the onset of diseases that are typically life-limiting in the elderly, such as cardiovascular disease and dementia. However, nearly one fourth of the centenarians studied demonstrated no significant presence of LAVs, suggesting other genetic factors could be involved or that environmental factors also play a consequential, but not yet determined, role.

Even if we come to understand well the genetic characteristics associated with exceptional longevity, we still don’t know whether genetic innovations would significantly extend our longevity. Genetic testing technologies have become very sophisticated: We can perform up to one million genetic tests over the short course of several hours through the use of biochips. Whereas there were perhaps 100 diseases for which genetic tests were available in 1993, today we have over 1,500.

One of the more potentially interesting genetic developments has to do with the early detection (and presumably treatment) of Alzheimer’s disease. A significant percentage of Alzheimer’s disease can be explained by genetic mutations associated with deposition of beta-amyloid in the brain. We now have brain scans that can show the presence of the beta amyloid protein associated with Alzheimer’s even before the development of mild cognitive impairment. An unprecedented number of drugs are now in clinical trials that could delay onset, slow progression and reduce symptoms of this fatal disease. However, these drugs generally do not directly address the genetic alterations involved with the development of Alzheimer’s, which is a polygenic disease associated with multiple genetic variations resulting in increased risk of disease.

It is highly unlikely that there will be streamlined therapy that will be effective against such polygenic diseases. More likely, effective future therapies would resemble the multiple drug regimens of cancer chemotherapy.

Since initial completion of the Human Genome Project about 10 years ago, the complexity of function of our genetic code has been discovered to be much greater than originally thought. Development of effective treatments for supposedly more straight-forward monogenic diseases has proven frustrating. Gene therapy and stem cell therapy still haven’t lived up to initial billing, and other aspects of medical advancements projected to result from our exploding knowledge in genetics still haven’t materialized. For example, we still don’t have useful clinical applications for pharmacogenetics, where the most effective drugs in treating specific illnesses are selected according to an individual’s genetic map. The age of personalized medicine, where health care is guided by an individual’s genetic makeup, still has not dawned, although it may be closer than we think.

One area where some advancement has been made is in the understanding and treatment of cancer, a disease associated with mutation of genetic somatic material (that is, DNA in tissues of the body that are not inheritable germ cell lines-sperm or eggs.)

For example, advanced malignant melanoma has been effectively treated with a drug, PLX4032, which kills cells containing a mutation that is involved in the development of most malignant melanomas. Unfortunately, the effects last for only about six months; but as research continues, longer durations of remission likely will be attained. Notwithstanding the significant potential for genetic-based improvements, there are still these mathematical limitations. It has been estimated that complete elimination of cancer would only increase life expectancy at birth by four years for males and three years for females.

So we must temper our enthusiasm for the potential impact of genetics. That is, unless it leads to an extension of what has not changed for at least 2,000 years-our ultimate biological age.

Michael Fasano is president and Robert W. Lund, M.D., is medical advisor of Fasano Associates, Washington, a life settlement actuarial firm.