"In this world nothing can be said to be certain, except death and taxes," quipped Benjamin Franklin. For now both remain inevitable, but two exciting new studies suggest that the grim reaper might be put off by novel treatments that can slow and even reverse aging.
Peter de Keizer, a molecular geneticist at Erasmus University, reports in the journal Cell that he and his colleagues have developed a technique that kills off senescent cells. Our bodies have two ways of preventing damaged cells from becoming cancerous: kill them off, or cause them to cease replication and thus become senescent. Senescent cells accumulate as we grow older, secreting inflammatory substances that harm neighboring cells and contribute to many age-related diseases, including atherosclerorsis and diabetes.
De Keizer and his colleagues have developed a treatment in mice that selectively kills senescent cells while leaving healthy normal cells alone. They discovered that old or damaged cells become senescent rather than die when the FOXO4 protein binds to the tumor suppressor gene p53. They have designed another protein that interferes with the ability of FOXO4 to halt p53 from causing cells to die.
De Keizer's team administered the new protein to both fast-aging and normally aged mice. The treatment worked as they had hoped, jumpstarting the ability of p53 to make senescent cells commit suicide. Eliminating senescent cells restored stamina, fur density, and kidney function in both strains of mice. The researchers report that they are continuing to study the rodents to see if the treatment extends their lifespans. They plan to try the treatment to stop brain cancer in human beings, but the ultimate goal is to treat aging as a disease. "Maybe when you get to 65 you'll go every five years for your anti-senescence shot in the clinic. You'll go for your rejuvenation shot," de Keizer told the Tech Times.
In the same week, another group of Harvard researchers led by molecular biologist David Sinclair reported in Science about experiments in mice that thwart DNA damage associated with aging and exposure to radiation. As we age, our cells lose their ability to repair the damage to the DNA that makes up our genes. The repair process is orchestrated by the SIRT1 and PARP1 proteins. Both proteins consume the ubiquitous coenzyme nicotinamide adenine dinucleotide (NAD) to operate. As we grow older, the amount of NAD in our cells declines, thus allowing another protein, DBC1, to inhibit the DNA repair activity of both SIRT1 and PARP1.
In their new research, the scientists fed the NAD precursor nicotinamide mononucleotide (NMN) to mice that were equivalent in age to an 80-year-old person. They also gave it to mice whose DNA had been damaged by radiation. The compound boosted NAD back to youthful levels and restored their ability to repair the DNA damage in both the old and irradiated cells. Sinclair said, "The cells of the old mice were indistinguishable from the young mice, after just one week of treatment." In addition, dosing astronauts traveling to Mars with NMN could counteract the damage that radiation in deep space would cause them. In an earlier experiment by Sinclair and his associates, the muscles of two-year-old mice fed NMN resembled those of six-month-old mice with respect to insulin resistance, inflammation, muscle wasting, and other important markers. Sinclair says that his group plans to launch human NMN trials in the next six months.
Other groups have already started and completed safety trials of other NAD precursors in human beings. Leonard Guarente, director of the Massachusetts Institute of Technology's Glenn Laboratory for the Science of Aging, reported the results in December of a clinical trial involving 120 people who took the NAD precursor nicotinimide riboside (NR). The trial found that subjects experienced no serious adverse events. The participants ranged in age from 60 to 80 years old and took it for eight weeks.
The researchers report that NAD "levels increased from baseline in whole blood by an average of 40 percent at four weeks and maintained that increase for the duration of the trial." These results will be submitted to a peer-reviewed journal soon. Guarente is the co-founder the startup Elysium Health, selling NR pills at $50 per month as a nutraceutical that is "designed to support well-being at the cellular level."*
Of course, researchers have developed all kinds of treatments that cure illnesses like cancer in mice that turn out not to work in people. So de Keizer sensibly observed to The Daily Mail, "I would also advise caution for claiming too much, too soon about the benefits of the fast-growing list of therapeutic compounds that are being discovered." Nevertheless, "these are clearly very exciting times, and I am confident we will find applicable anti-senescence treatments that can counteract age-related pathologies." Back in 2005, Sinclair said he "would be disappointed if we were all born one generation too early." Hurry up—none of us is getting any younger.
*Disclosure: I started taking Elysium's NR supplement about two months ago. It's hard to tell but I may be experiencing some uncomfortable gastrointestinal side effects, so under no circumstances should readers consider this as any kind of endorsement.