Age is by far the biggest risk factor for heart disease. It’s seven times more important than high cholesterol.
CEO of the Buck Institute
A Decade Later
These scientific investigations into the biochemical pathways of aging have moved incredibly fast from the lab to commercialization.
Scientists have recognized since the 1930s that mice on calorie-restricted diets can live 2x longer. It’s shown to work in every species studied. We just didn’t know why it worked or how to safely take advantage of it. Gradually, science has drilled down on the metabolic and cellular mechanisms. A rhesus monkey at the University of Wisconsin is living to the human equivalent of 130 years old on a calorie-restricted diet.
The research on how calorie restriction slows aging has drilled down to the metabolism coenzyme NAD+, which regulates the sirtuin class of cellular mechanism proteins, critical to DNA repair. NAD+ is a coenzyme found in all living cells, but it declines with age. Just putting drops of NAD+ into mice’s drinking water led to obvious age reversal within a week. The muscle tissue of 2-year-old mice soon had qualities identical to that of 3-month-old pups. Trials in humans are in the recruiting stage, and will focus at first on brain repair after a mild concussion.
Old people have just as many stem cells as young people—so why don’t they work just as well? In search of the answer, in 2005, Thomas Rando at Stanford connected two mice together, an old mouse and a young one, to share a circulatory system. Quite simply, the old mouse grew younger—because compounds in the young blood reactivated the stem cells of the old mouse, triggering tissue genesis. A race began to find exactly which compounds in young blood are at work.
When a cell’s chromosomal telomeres shorten to the point it can’t divide anymore,
Unity Biotechnology in San Francisco has developed a drug that causes zombie senescent cells to die. In lab tests of their drug, human knee stem cells regain their ability to regrow cartilage. Clinical trials have begun.
Meanwhile, the compound rapamycin is already FDA approved. It’s used to temporarily suppress the immune system after organ transplants, but it also blocks senescent cell signaling. By loading nanoparticles of rapamycin into molecules that bind only to senescent cells, we can silence them—without suppressing immune cells.
Telomeres are the caps on the end of our chromosomes. Every time a cell divides, the cap shortens. After 50 to 70 divisions, the cell will die because there’s no telomere left. However, the enzyme telomerase works to replace and repair the caps, allowing the cell to divide without limit. For their work on the discovery of telomerase, Elizabeth Blackburn and Carol Greider were awarded the Nobel Prize in 2009.
Several studies involving mouse-to-mouse blood transfusions have demonstrated confirmed antiaging effects. To make the jump to humans, researchers started by injecting mice with young human plasma (from teenagers or from umbilical cords of newborns). The infusion doesn’t just boost the recipients physically, it also improves their cognition and memory. This brain boosting has been connected to the TIMP2 protein present in plasma.
Now human-to-human plasma transfusions have begun. A trial is under way at a hospital in South Korea to test whether injections of human umbilical cord plasma have antiaging effects in older healthy people. The Silicon Valley startup Alkahest has found no safety concerns using teen blood plasma in Alzheimer’s patients, and is now looking at its efficacy.
Gene therapy that targets telomerase is yet a fourth approach. Essentially it gives the renewal power of stem cells to other cells. While not yet tested in humans, it’s had a remarkable effect on aging mice, delaying or reversing osteoporosis and insulin sensitivity, and improving muscle strength and coordination. This approach had been considered dangerous because, presumably, it might make cancer cells immortal, too. However, scientists have successfully found a way for this gene therapy only to target slowly dividing cells, opening the door to a permanent solution to prevent cellular senescence.
Sperm and eggs from older people still have the power to create a brand new baby. The genetic capacity for youth is in us all. Learning from that, we can trick our cells into thinking they’re younger than they are.
Nobel Prize winner
How will society be shaped by this field of science? The ramifications are vast.
Because the FDA does not currently consider aging itself a disease, the approved uses in the next 10 years will be restricted to very specific conditions. Nevertheless, the word will get out that these interventions might have a universal benefit. Their off-label use will produce a highly charged debate as patient advocacy groups clamor for their “right to try.” As always is the case, the supplement industry will cash in, touting their precursor or building block’s miracle effects.
In the meantime, the benefits of plasma transfusion will mean 25 “blood vacations” at medical spas will be popular. It could also lead to “blood farms,” where young people in poor countries get their blood harvested for use abroad. But the likelihood for corruption in that kind of system is huge. The research to create synthetic blood will accelerate— scientists have already figured out how to make red blood stem cells fly past their normal 50,000 production limit.
If the FDA removes black box warnings on any treatments, such as TIMP2 or NAD+, we will see an explosion of clinics offering antiaging solutions. Their use will be elective and not covered by insurance, exacerbating the gap between rich and poor that has already widened considerably since the 1970s.
Young working couples will no longer feel like they are in a race against time, trying to advance their careers and bear children before they are too old. Parents will be con dent they can use assisted reproductive technology to have children later. Orthopedic stem cell technology will mean they can coach the kids’ little league soccer teams as 60-somethings. Knowing they can keep working longer and afford more children, the birth rate for high-income families will go up, while the birth rate for low-income families will go down.
Older professional athletes are certain. Golf and tennis more so than other sports, because cognitive control under pressure is most critical in those contests. Triggering the ability to regrow cartilage or heal muscle damage faster won’t be considered “doping.” Better fitness regimens have already put us on this path. In 1990, half the women tennis players in the year-end Top 10 were teenagers during that season. Currently, there are only three teenagers in the Top 100.
Rather than retiring, waves of people will consider a full career change at midlife—including going back to school—because they know they’ll live far longer. Many colleges will create branches in urban centers focused on adult reeducation degrees. And because the aged often face age discrimination, we will celebrate start-ups that are committed to hiring these self-remade graduates.
It will bankrupt Social Security, but not Medicare. When Social Security was created, in 1935, life expectancy was only 62. The number of people over age 65 will balloon. But this won’t hurt Medicare, and in fact it will help it— because people over 65 will have a lot less heart disease, diabetes, cancer and Alzheimer’s.
Three- and four-generation households will become far more common, because we won’t need to send the grandparents to assisted living centers where medical treatment is on site. They’ll be healthy enough far longer. Real estate developers will need to take this into account. Grandparents will become an even more common solution to childcare for working couples, and “grandparent quality” will become a bigger factor in choosing a marital partner. Reducing the stress of marriage will lower the divorce rate when children are still at home.