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WorldVIEWPoint: Aging 2.0

WorldVIEWPoint: Aging 2.0

Stem cells and digitized DNA may hold the key to high-performance longevity



Although we can’t live forever, we can aspire to live much longer and healthier lives. In fact, living well into our 90s lies just ahead, if we keep fine-tuning the right tools. We start by understanding that aging arises from an accumulation of defects in our biology, and this causes joint decay, decreased muscle mass, Alzheimer’s and so forth. With digital health—basically, using high-performance computational tools to study complex biological processes—we can interrogate the cellular and molecular events that occur during human aging, and identify those that can be controlled or modified to slow or arrest those that degrade or degenerate our bodies over time. To make the most of digital biology, I joined forces with my friends and colleagues—Craig Venter and Peter Diamandis—to form Human Longevity, Inc. (HLI).

At HLI, we combine knowledge from many areas of biology—the genome, proteome, biome and more—with advanced approaches to computing and informatics, all to create sophisticated cellular therapies. To build these treatments, we are collecting data on genomes and health outcomes from people around the world. All of that information will be combined to build powerful cellular therapies—actually developed from enhanced human cells—that will battle cancer, diabetes, obesity, heart disease, dementia and more. Further, these treatments will keep our bodies and minds performing as if they were younger and for a longer time.

Fundamentally, this work depends on making the most of tools that our bodies already possess, and I started thinking about these tools years ago.

From Trash to Treatment
Early in my medical career, I specialized in the treatment of head and spinal cord injuries. With one patient, a defect in the tissue that surrounds the brain, the dura mater, needed to be repaired after a serious head injury. I realized, from my ob/gyn rotation, that the amnion—this amazing, clear plastic-like tissue that surrounds an embryo—looked a lot like the tissue around the brain that I needed to replace. That moment spawned other ideas about biological tissues being used in new ways. In particular, I started thinking that the placenta—the leftovers of birth—could be used as a source of stem cells. Instead of just throwing away the placenta after birth, we could make use of it. My personal “eureka moment” led me to form Anthrogenesis, which later became Celgene Cellular Therapeutics, where we mined the placenta as a source of stem cells that can be turned into treatments.

A stem cell carries the remarkable capacity to participate in renovation or repair at any place in the body. Moreover, we can get these cells from many places beyond the placenta, including bone marrow and even fat tissue. Stem cells all “think” they are still in a fetus, and that is perhaps the most regenerative environment of all. In fetal surgery, for instance, you can open the uterus early in a pregnancy, perform surgery on the fetus, close up and let the baby come to term—and you won’t see a scar. You won’t see any evidence of the surgery at all. So a fetus can repair and renew itself. What’s fueling that ability? Stem cells.

These same cells keep us healthy in our youth. Over the years, though, this regenerative “engine” runs lean on fuel, the stem cells. As that happens, the defects of age start to accumulate. In addition, stem cells orchestrate our response to injury, making them perhaps our best defense against disease. The susceptibility to disease thus increases as we age.

Repository of Repair
How can stem cells fix things? It’s in their DNA, which forms a repository of synthetic repair. Every stem cell contains information, in its DNA, that codes for the production of molecules that guide the signaling and synthesis behind all of the steps that make tissues and organs. In this process, a primordial stem cell undergoes a series of cellular divisions that make it more specialized at every step. We can watch such a change under a microscope, as this primordial cell turns into a heart cell or a neuron—all depending on its surrounding environmental cues that drive the DNA to create different things.

This DNA makes up a sort of biological software. Like lines of digital code, the genes in the DNA can be processed to drive an action, like generating a protein. As a stem cell develops into a specialist like a neuron, though, it loses the ability to be anything else. That neuron, for example, can’t turn on the genes that make a heart cell. And this is what happens as our cells age—they lose their versatility. At some point, we lose the ability to rejuvenate.

As we gather data on human genes and the outcomes that they create, healthcare experts can turn that knowledge into treatments for disease and to fight ordinary aging. In short, we must find ways to replenish the regenerative engine, and we do that by replenishing the reservoir of stem cells that provide synthetic versatility.

With this knowledge, we can identify defective products—cells or tissues or organs—and then use stem cell–driven synthesis to restore the function of those parts. Doing this, though, depends on a deep understanding of how the biological software, a stem cell’s DNA, drives repair in its youth and loses that ability with age. So by better understanding aging and the molecular changes that drive it, we can learn to slow it down or work around it in places. We can find ways to use stem cells—maybe our own, those from someone else or from a placenta—to control certain diseases or to restore functionality as we age.

The future of stem cells and the future of cellular medicine will benefit from this analogy with computers and digital processing. Your software, your biological software, that is, resides in the nucleus. It’s not that different than having binary code that resides in the memory access of a computer. This thinking leads us to the concept of reprogramming the biological software of stem cells, which is already happening in activities to create induced pluripotent stem cells. These tools provide a platform for controlling fate and function, and they have broad biomedical applications. The most exciting one to me is prolonging and extending the quality of life.



Robert Hariri is the founder and chairman of Celgene Cellular Therapeutics, where he turns stem cells into therapies for many diseases, cofounder and vice chairman of Human Longevity, Inc., and founder and chairman of Myos Corporation, a company developing products that improve the health of muscle. He trained as a neurosurgeon, is an avid jet and high-performance aviator and has produced several feature films and documentaries.
 


 
Opinions expressed in worldVIEWpoint do not necessarily reflect those of the editors.

 

Illustration by Alex Nabaum

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