Blog 29 New Approach to Aging by award-winning author, adventurer and scientist Mark Kingston Levin PhD
Cellular senescence (deterioration from age) is a condition where normal cells cease to divide. In the early 1960s, biologists Leonard Hayflick and Paul Moorhead made a great discovery that normal human cells divide approximately 50 times before they stop. This phenomenon is known as “replicative senescence,” or the Hayflick limit. Hayflick’s discovery that normal cells are mortal overturned a 60-year-old dogma in cell biology. Hayflick found that the only immortal cultured cells are cancer cells.
Figure 1. The typical normal human fetal cell will divide between 50-70 times before experiencing senescence. As the cell divides, the telomeres (compound structures at the end of a chromosome) shorten. The Hayflick limit is the limit on cell replication imposed by the shortening of telomeres with each division. This end stage is known as cellular senescence.
As we get older and wiser we also suffer cell impairment. Damaged cells stop dividing to produce new cells. These senescent cells accumulate in various tissues of the body. Although no longer dividing, these cells are still alive and secrete compounds that can harm the tissues around them. Research suggests that the buildup of senescent cells over time may increase the likelihood of health problems. This is a major factor in aging.
Figure 2. Drs. Laura Niedernhofer and Paul Robbins of the University of Minnesota Medical School were key players in developing new methods to test drugs for anti-aging properties.
Researchers Paul Robbins and Laura Niedernhofer devised a means to test new and exciting drugs, called senotherapeutics, that combat senescent cells in animals. By removing senescent cells from the body, these new drugs have shown promise in prolonging a healthy lifespan, or healthspan. Results were published in Nature Communications on September 4, 2017, funded in part by the National Institute of Health (NIH).
The researchers used mouse cells known to quickly break down under certain conditions. They developed an approach that could identify the senescent cells. By comparing the number of senescent cells with total cells, the method could identify compounds that both suppress senescence and selectively kill senescent cells, labeled “senolytic” (from the words “senescence” and “lytic” – destroying).
The team screened nearly 100 compounds known to regulate the process that breaks down and recycles waste within our cells. This recycling process, called autophagy (“auto” – self + “-phagy” – eating), has previously been linked to aging and reduced lifespan.
Further testing confirmed that two of the senolytic compounds, geldanamycin and 17-AAG (tanespimycin), efficiently killed senescent cells without significantly affecting healthy ones. Both inhibit a protein labeled heat shock protein 90 (HSP90). HSP90 plays an important role in protein recycling and may be involved in cancer.
“Our screening platform already has identified multiple classes of compounds that extend healthspan in animal models,” Robbins said. “Right now, we have a pipeline of compounds that should be even more effective than the ones in this study.”
These results demonstrate the ability to find compounds that combat symptoms of aging. However, careful study in humans is required to discover any possible adverse side effects before we can use them.
Mark Kingston Levin PhD award-winning author, adventurer and scientist.
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Dr. Levin was born and grew up in Vermont with many winters spent in Florida as a child. As a teenager he wrote poetry, served as a lifeguard and played football. He currently enjoys sailing, exploring underwater caves, snorkeling, writing science fiction and other pursuits. After working on the Apollo and Mars projects, he returned to school to study under Nobel Laureate Paul Dirac, obtaining his PhD in 2.5 years. Dr. Levin founded two companies and served the science policy apparatus in President Ford’s administration. He has been published over 44 times in scientific literature and was awarded over 32 US patents. The science fiction writer is now emerging with his first work, a trilogy entitled 30th Century. The first award-winning book, 30th Century: Escape, is currently available on Amazon. Book two in the series, 30th Century: Revived, was released April 29, 2018. It is now available on Amazon, Barnes & Noble, and other retailers.