We’d like to think we’re going to live forever, but realistically speaking, that’s…well, unlikely. In 2016, American life expectancy declined for the second year in a row, per data (link opens a PDF) gathered by the National Center for Health Statistics. That’s largely due to various worsening health problems like heart disease and stroke. In any case, the news is pretty grim; the average American will live to be 78.6 years old, a whole two decimal points fewer than in 2014. Women can expect to live for about 81.1 years, while men can expect to live a measly 76.1. Nobody likes to think about getting old, but that’s exactly why some scientists are obsessed with the concept. Someday, we might be able to slow down the aging process or even halt it entirely—and, according to a recent research review, that day might come sooner than we think. The piece, which was first published in The Journal of American Geriatrics, attempts to evaluate the clinical potential of senolytic drugs. A team led by James L. Kirkland MD, PhD, outlined testing guidelines for senolytics (and yes, we’ll explain exactly what that means in a moment). These drugs would be the first substances designed specifically to target the aging process, and if they’re effective on humans, they could change the way doctors treat age-related diseases (and make parking at Denny’s much more difficult). Before you break out the sparkling grape juice and celebrate, we should note that we’re a long way from turning society into some sort of elder-run utopia. We don’t have proof that senolytics work, and if you’re hoping to head to your local supermarket and pick up a big bottle of senolytic pills, you’re going to be disappointed. The purpose of the paper was merely to establish practices for clinical trials. Still, the authors note that medicine that targets fundamental aging processes “could transform geriatric medicine by enabling prevention or treatment of multiple diseases and functional deficits in parallel, instead of one at a time.” In other words, instead of treating diseases linked to aging, like Alzheimer’s or cancer, doctors would target aging itself. We decided to look into the science to try to determine whether a magical anti-aging pill is really right around the corner. Hint: It’s complicated.
Buckle up: Here’s how proposed senolytic drugs would work.
Senescence occurs when a cell stops dividing; it essentially dies but remains in the body. Senescence is thought of as a natural part of the cell aging process because, if cells replicated forever, they’d eventually become cancerous. “The purpose of this … is to make sure that these cells do not maintain their damaged genomes any further in the organism,” Ira Pastor, CEO of regenerative medicine company Bioquark and member of the World Economic Forum’s Human Enhancement Council, tells HealthyWay. The problem is that senolytic cells don’t just disappear after they’ve stopped working. They hang around and secrete signals called SASPs (senescence-associated secretory phenotype, in case you’re studying for an advanced biology test), which tells the body to get rid of them. Those SASPs also contribute to the various negative processes we associate with aging. Eventually, the body eliminates the senescent cells, but by that time, the damage is done. As we get older, our bodies become less efficient at getting rid of the senescent cells, feeding the aging process. “The core belief … is that as we get older, and as the elimination of these senescent cells is slowed down, the SASP secretion is detrimental to the surrounding tissues and can cause a range of other problems, such as inflammation, tissue damage, and degeneration, therefore speeding up aging processes,” Pastor says. That’s where senolytics come in. “Senolytic therapeutic substances are being developed to see if it is possible to selectively induce [or] enhance the elimination of these senescent cells from the body.” Senolytic substances could potentially compel the body to speed up its elimination processes, turbocharging the garbage collection and allowing us to stay young, fit, and beautiful forever (or at least slightly younger and fitter than we’d be otherwise). That all sounds pretty good to us. Unfortunately, the aging process isn’t exactly simple, and scientists don’t think of cell senescence as purely bad—or good, for that matter. Yes, this next section is a bit of a bummer.
There’s a pretty strong argument against senolytics.
Here’s the thing: Cell senescence is complicated, and it’s not exactly spontaneous. “It is important to understand that senescent cells don’t just pop up out of the blue,” Pastor says. “There is a whole ‘upstream’ system of tissue-level architecture dynamics—tissue membrane potentials, forces of mechano-transduction, signals from the microbiome, visco-elasticity of interstitial fluids, molecular crowding/variability, etc.—that controls their production and deposition.” Dizziness aside, here’s what we got out of that: Senescence isn’t a random occurrence, and getting rid of the senescent cells won’t necessarily stop your body from producing them. “Just like we are now understanding that cancer is no longer just about random single cells that have ‘forgotten to die,’ but more of a tissue-level disease that produces cancer cells, the same can be said for senescent cells,” he continues. An article by Jan M. van Deursen, first published in the journal Nature, supports the idea that senescence is a multifaceted process—and, at times, an extremely useful one. “It’s also important to understand that senescent cell bio-dynamics are also very beneficial in many facets of our life and in keeping us alive,” Pastor says. “Aside from being beneficial in preventing cancerous transformation, they are important in human wound-healing dynamics, certain components of human regeneration, and—probably most importantly—in various aspects of tissue patterning, especially during embryonic development.” Wait, embryonic development? That seems kind of counterintuitive if senescence is associated with aging. “Paradoxically, embryos are full of senescent cells during their development, and this represents the exact opposite of aging, where the new fetus is becoming more robust and resilient,” Pastor says. This is a type of programmed senescence; during normal development, embryos produce a high number of senescent cells, which allows them to remodel their tissues. To put it plainly, you wouldn’t want to eliminate senescence entirely.
With that said, there’s still some hope for the therapy.
At this point, the arguments on both sides of the issue are pretty much theoretical, but experiments are underway to determine whether stopping senescence can extend health in old age. Some animal testing, reported Scientific American, indicates that senolytic substances are safe and potentially effective in mice, but Pastor believes that those studies are misleading. “Humans never experience the ‘flood’ of senescent cells in our bodies that are seen in the genetically engineered animal models,” he explains. “We have actually very few at any given point in time, as our bodies are very good at getting rid of them.” “So, ultimately, I believe that it is not the senescent cells that are causing these diseases of aging, but the actual reverse: In diseased tissues, senescent cells are being created or ‘hijacked’ as part of the grander disease and pathogenic tissue remodeling processes, orchestrated from many other factors which truly represent a complete process of biological aging.” Therefore, eliminating senescent cells might not be effective in humans, since our bodies will quickly replace them. “Our belief is that just killing them off faster will probably not do much beyond opening up space for more to be created. One still needs to turn off the disease processes upstream that are causing their formation in the first place. Still, time will tell which approach is correct.” We should note that Pastor’s view isn’t universally shared among scientists; the aforementioned Scientific American piece points to the fact that some believe removing senescent cells will cause the body to create new tissues, thereby slowing down the aging process.
For now, the best way to slow the aging process is pretty straightforward.
Unfortunately, our advice isn’t as exciting as “take this medication and enjoy decades of brilliant youth.” At this point, the only ways to reduce the effects of aging are to get plenty of sleep, eat well, exercise, and wear plenty of sunscreen. There’s even some research that suggests drastically reducing caloric intake for a few days a month can help extend your lifespan. Note, however, that even the researchers behind these findings don’t recommend extreme changes in what you eat for any length of time. “Life is difficult enough without engaging in some bonkers diet,” Rozalyn Anderson, a co-author of one of these studies, told Scientific American. “We really study this as a paradigm to understand aging. We’re not recommending people do it.” We’ll go a step further and recommend against it. Aging is the decline of health; if you want to fight it, it’s best to practice healthy habits. Unfortunately, the visible effects of aging rely on your genetic profile, so for the time being, there’s not much else you can do—but if senolytics do turn out to be an effective form of therapy, that could change in a hurry. “In the coming years, we will see whether this strategy of increasing their elimination impacts human diseases and thus healthy aging,” Pastor says. “[At Bioquark], we do not much believe in the concept.” Still, human trials might begin sooner rather than later. If senescence really is the gateway to the real-life Fountain of Youth, it’s an exciting time to be alive (and, more importantly, to continue to be alive).
