Cell Research Taps into Fountain of Youth

A new breakthrough in anti-aging research could lead to gene and stem cell therapies that turn back the hands of time.

by Michael MacRae
February 05, 2018

The search for the Fountain of Youth never gets old. Throughout history, humans have sought in vain to stop the clock on aging – or at least the outward signs of it – with make-up, plastic surgery, and dubious patent medicines. Now, however, a promising new twist in the fight against old age could propel the field of aging research beyond its snake-oil image. Recent breakthroughs in genetic and cellular research have revealed surprising new biological details of the body’s remarkable ability to rejuvenate itself, findings that may give humans a real measure of control over how long and how well they live.

“Healthspan” is the go-to buzzword for researchers and drug makers careful not to imply that they’re working toward eternal life. Rather, the stated goal is to help people achieve the longest, healthiest lifespan their biology will permit. The term acknowledges that we all age and eventually die, but suggests it will one day be possible to do so without the diseases, infirmities, and mishaps that cause disability, morbidity, and premature death.

The Worm Turns

The most recent headline-making, anti-aging discovery comes from researchers at Calico Life Sciences (South San Francisco, CA), whose experiments with C. elegans roundworms and frogs have revealed a chemical switch that apparently triggers cellular repair and rejuvenation. If this obscure biological mechanism can be found and exploited in humans, this discovery could have significant implications in the fight against a wide range of age-related conditions.

Because C. elegans and humans share many of the same biological mechanisms of cell division and cell death, the species is a powerful model for human health and disease research. Led by Cynthia Kenyon, Ph.D., vice-president for aging research at Calico, a Google-funded R&D firm, the group had previously found a number­­ of genes in C. elegans that play a role in cell repair. By switching these genes on and off, they were able to double the worm’s lifespan. And as is true with humans, these worms’ cells develop accumulations of deformed proteins throughout life. The abnormalities are perpetuated as cells divide, eventually causing the wear and tear of old age. The rules of reproductive biology, however, prevent these deformities from being introduced to future generations of offspring. Through a process known as proteostasis, the cells renew themselves by getting rid of clumping proteins before they can be passed down. There are many questions how a species’ germline is kept immortal, but the Calico group may have answered one of them.

In their recent paper published in Nature, the team described a remarkable cell-rejuvenating event during the worm’s reproduction process. The new work breaks down the steps of an intricate process by which mature oocytes rid themselves of these abnormal protein masses when sperm approaches en route to fertilization. The scientists speculate that the sperm cells transmit a chemical signal that stimulates motion in the protein clumps and causes them to be captured by bubble-like structures in the oocyte called lysosomes. The sperm signal also creates an increasingly acidic environment within the lysosome, which destroys the proteins. The oocyte then converts what’s left into fuel. As a consequence, the proteins are not passed down to the worm’s progeny and the species’ germline remains immortal through the generations.

In experiments with frogs, which are even more biologically similar to humans, Kenyon’s team observed some of the same chemical signaling events that signify this cell-cleansing step in roundworms – a further indicator that similar forces may be at work in human cell biology. One of the most intriguing questions posed by this finding is whether or not lysosomes contribute to a similar self-cleansing process in human stem cells. If a chemical trigger to self-repair can be found in stems cells rather than through the reproductive process, it would open the door to treatments for a wide range of diseases that impede quality of life in people as their tissues lose their self-rejuvenation abilities.

The Calico team cautions that their work is at a very early stage and its eventual commercial applications, if any, are a long way off. However, the breakthrough is a clear example of how scientists across many disciplines are closing in on bona fide, science-based approaches to prevent, slow down or reverse the underlying causes of age-related decline and disease.

Preparing for an Audience of Everyone

Scientists are developing treatments in every therapeutic category, from traditional small-molecule drugs to the latest in gene-transfer therapies, as well as exploring immunotherapies, nutritional supplements, genetically modified foods and more. For the drug industry, anti-aging products in principle would be marketable to everyone – not just people with a particular disease. Not surprisingly, analysts are forecasting robust annual growth in the global anti-aging drug market – anywhere from 5.8% to 8%, with the potential to surpass $331 billion by 2021 by some estimates.  With big players like Novartis and a number of well-financed start-ups in the game, it’s safe to assume engineers will be in demand to help scale-up and optimize a wide range of manufacturing processes as more anti-aging therapies come on line.

Apart from the inevitable ethical hurdles a proposed “cure” for old age would face, the science is still in its infancy. A commercial drug that can in some way slow down or reverse the aging process is likely a very long way off. But in an era where gene therapies are now in clinical use and scientists have applied new techniques like CRISPR to repair disease-causing genes in human embryos, it’s probably none too early for bioengineers to start thinking about the practical implications of aging research.

Michael MacRae is an independent technical writer based in Portland, OR.

Read more about Cell Therapy on AABME.org.