We’re constantly reporting on new research breakthroughs in the biology of aging — trying to figure out, and hopefully slow down or even reverse the aging process at the cellular level. As exciting as these reports are, they almost always end with some caveats: these are just animal models, they still have to be validated with human trials, it will take some time, etc., etc.
Fair enough. But how are things going?
Here’s a timely and valuable update, based on a review published in Cell Metabolism by three leading researchers: David Sinclair of Harvard, Leonard Guarente of MIT and Guido Kroemer of Université Paris Descartes.
They reviewed the current state of play in human trials of “potentially geroprotective drugs,” or drugs which may prevent the development of aging-associated conditions. They covered eight categories. We urge you to read the article, because it’s fairly detailed (and technical), but here is a brief summary:
Metformin – Already widely used to help diabetes patients (although the exact mechanism is still not 100% clear), its anti-aging potential was identified in a 2014 study indicating that diabetes patients on metformin lived longer than age-matched healthy people. Was that really true? “So far, in human trials, metformin has been shown to protect heart function in diabetics, improve immune function (in a small-scale trial), and lower one marker of inflammation (CRP), but not another marker (IL-6).”
NAD+ and sirtuins – “NAD+ is a ubiquitous and multi-purpose molecule that mediates energy production and serves as a substrate for the family of enzymes called sirtuins. Sirtuins play various roles, including in DNA repair and mitochondrial maintenance, and their activation has been shown to extend lifespan in numerous animal models. In addition to NAD+ supplementation, some sirtuins can be activated directly by compounds such as resveratrol, quercetin, and fisetin.” In human trials, NAD+ precursors NMN and NR “led to higher physical performance and lower biological age in middle-aged adults.” NR trials in patients with Parkinson’s, Alzheimer’s, or ALS “have shown some promise, and more trials are currently running.”
GLP-1 – GLP-1 is a hormone “known to stimulate insulin secretion and mediate satiety.” GLP-1 receptor agonists (chemical sustances that bind to, and activate, receptors) have become popular due to their effectiveness in promoting weight loss. Given the association of diabetes and obesity with aging, they therefore “have the potential to be highly effective anti-aging agents.” Two large trials have shown improved cardiovascular function and decreased cardiovascular mortality, while two other studies have demonstrated positive effect on Parkinson’s patients.
Rapamycin and mTOR – FDA-approved rapamycin is used as an immunosuppressant and has also “been found to extend lifespan and healthspan in various animal models, including mice, even when given late in life.” It works by suppressing mTOR, a protein complex that mediates cell growth. It has been “shown to reduce a subset of pro-inflammatory T cells in lupus and to cause some skin rejuvenation.” There are apparently some side effects issues, which might make it “ill-advised for people with highest levels of physical activity.”
Spermidine – Spermidine is a metabolite that is known to induce autophagy, the process “of clearing out accumulate cellular junk.” Two studies have demonstrated cognitive improvements. Since it’s found in food, population studies are possible, and two studies — from Italy and Austria — reported an inverse correlation between spermidine intake and mortality.
Senolytics – This is a whole new class of drugs that didn’t even exist several years ago. “They supposedly clear out senescent cells – those that became dysfunctional and stopped proliferating, but remain in the body, causing inflammation and other types of harm.” Do they work? There are still very few human trials. Some do show the ability to clear out senescent cells, but there have also been some failures.
Probiotics – “Probiotics have been demonstrated to improve immune function, increasing the number of T cells and lowering the number and duration of common infectious diseases. Several studies have reported that a healthier microbiome can improve cancer outcomes… Probiotics can also lower inflammation and improve cognitive function.”
Anti-inflammatories – A huge category, because “chronic inflammation is one of the hallmarks of aging.” Research trials deal with cytokines, proteins that help control inflammation; most of the completed trials involved a cytokine called IL-6. “Reducing its level has been shown to improve the symptoms of irritable bowel syndrome and ulcerative colitis.” On the other hand, there can be negative effects that researchers are watching for.
What’s important here, from the perspective of a SuperAging layman, is that so much activity is going on, and the underlying science does seem to be pointing toward actionable outcomes — i.e., therapies that can be shown to be effective for humans. The article ends on a very upbeat note: “We believe that the next few years will present a tipping point, when the most viable approaches will become evident and move us toward a more widespread use of interventions targeting aging processes. While aging is not a disease as prescribed by the FDA, one might expect approval of these interventions to treat aging-fostered diseases.”
You can depend on us to keep you up to date on what’s happening now, and where it’s going.
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