This article was first written for The Montreal Gazette.
According to the Chinese biotech startup Lonvi Biosciences, the answer is “yes.” Referencing a study published in the high-quality journal “Nature Metabolism,” the company’s Chief Technological Officer claims that “living 150 years is entirely practical and may soon become a reality.” All it takes is downing a capsule of “Procyanidin C1 Senolytic Complex 1 (PCC1)” three days every month. Formulated from grapeseed extract and termed a “senotherapeutic” or “synolytic,” PCC1 is said to extend life by selectively killing senescent or “zombie cells.” These are cells that have stopped multiplying but have not died. They accumulate with age and secrete inflammatory compounds that drive tissue damage and precipitate age-related diseases. PCC1 (which is not your health food store grape seed extract) should therefore extend longevity. And it does. In mice!
Therein lies the problem. Mice are not men and any extrapolation from a mouse study to humans is highly speculative. At this point, promoting PCC1 supplements without any evidence from human clinical trials is jumping the gun. The “live to 150” claim is based on a naïve extrapolation from results seen in old mice after start of treatment. Whether PCC1 eventually becomes a viable anti-aging intervention or ends up as another blind alley leading to the elusive fountain of youth remains to be seen.
That blind alley is cluttered with failed life extension regimens. Way back, the ancient Chinese noted that mercury does not decay and used it to formulate various anti-aging elixirs. Bad idea. Emperor Qin Shi Huang reportedly died in 210 BCE at the age of 49 after consuming mercury pills intended to grant him eternal life. The Romans believed the blood of fallen gladiators would restore youthful strength, and alchemists in the Middle Ages reasoned that since gold never tarnishes, drinkable gold would help the human body resist aging. However, metallic gold does not dissolve in water, so they developed a process to produce soluble gold chloride by treating gold with aqua regia, a mixture of nitric and hydrochloric acids. Unfortunately, gold chloride can be toxic! When researchers examined the remains of Diane de Poitiers, King Henry II of France’s mistress, they found levels of gold 500 times the normal amount and concluded she likely died of chronic gold poisoning.
When it comes to anti-aging, the late 1800s and early 1900s have been referred to as “The Age of Glands and Testicle Juice,” alluding to the craze for testicle extract injections and monkey gland transplants sparked by the antics of neurologist Charles Brown-Sequard and surgeon Serge Voronoff. Brown-Sequard claimed greater vigor, mental clarity and improved erections after injecting himself with an emulsion prepared from dog and guinea pig testicles. Although the results were most likely due to the placebo effect, Sequard’s self-experimentation did foreshadow current treatment with testosterone. While no fountain of youth, testosterone therapy can be helpful if low blood levels have been properly diagnosed. Voronoff stretched Brown-Sequard’s idea further, grafting slices of monkey testicles onto the testicles of aging men. This, he believed, would slow senility and restore strength, memory and sexual function. He was wrong.
More recently, various vitamin and plant-derived antioxidant concoctions have entered the longevity sweepstakes, but no supplement has convincingly extended human life in randomized controlled trials. Pharmaceuticals have also jumped into the fray with some promise. Metformin, a diabetes drug, resveratrol, an antioxidant found in grapes, vitamin B3 and other such boosters of nicotinamide adenine nucleotide (NAD), the immunosuppressant rapamycin, and senolytics such as quercetin and fisetin extracted from fruits have some potential to counter aging according to pilot studies. However, recommendations made by marketers are essentially based on a premature extension of interesting lab results to humans.
So, is there anything that has been proven to increase longevity? Yup. It should come as no surprise that a combo of regular exercise and a proper diet, mostly plant-based with 1-1.2 grams of protein per kg body weight, will do it. But what else? In animals, from mice to chimps, calorie restriction has consistently been shown to increase longevity. How about in humans? We get some indication from the CALERIE trial (Comprehensive Assessment of Long-term Effect of Reducing Intake of Energy) that was designed to study the effects of calorie restriction in people. The plan was to cut calorie intake in some 200 non-obese subjects for at least two years and look for any signs of reduced aging. Even though the subjects were given specific instruction on how to achieve a 25%, calorie deficit, they only managed to cut their intake by 12%.
Several tests of biological aging were then conducted, including measuring the length of telomers, those bits of DNA at the ends of chromosomes that prevent the loss of genetic information when cells divide. With age, telomers are shortened and that can lead to cell senescence or even apoptosis, the self-destruction of cells when they can no longer divide safely. Overall, that means fewer fresh cells to replace old, damaged ones. That’s aging. But the CALERIE trial did not find any shortening of telomers with calorie restriction.
However, when “DNA methylation, another measure of aging, was examined, an effect due to calorie restriction was detected. DNA is commonly referred to as the “blueprint of life” since it provides the instructions for the synthesis of proteins that in one way or another govern life. Those instructions, though, can be altered by the attachment of single carbon fragments called methyl groups (CH3) to DNA molecules. Depending on the location of the attachment, such “methylation” determines which genes in DNA are turned on or off, and that in turn determines which proteins are produced. Methylation goes on all the time according to the body’s needs, but with aging, methylation takes a negative turn and shuts down genes that code for proteins needed for cellular repair. Lack of repair is characteristic of aging. On scrutinizing methylation data in CALERIE, researchers estimated a 2-3% slower pace of aging, potentially adding several years to life, comparable to giving up smoking.
Where does this leave us? With the good old sage advice, eat less and exercise more! But I will keep an eye out for results of the human trial with Lonvi’s grape seed senotherapeutic which is apparently now underway.
