Chapter 186
Changing Aging — 23
That’s where the Cellular Senescence Network (SenNet) can kick in to provide a panel of markers that may increase the efficacy of senolytics. It is still early in the human assessment of senolytics, but some promising early data suggest these may ultimately provide some benefit. An alternative route to clearing cells is revving up the waste removal from cells by promoting autophagy, through molecules like spermidine, urolithin A, or the function of mitochondria or lysosome subcellular organelles. It’s a pathway that has panned out in small animal models but without clinical trial corroboration to date.
Is there a marker of old age more infamous than menopause? As the organ clock data indicated, estrogen replacement was associated with slower aging across many organs, especially the immune system, brain, liver, and arteries. We’ve long known that menopause is linked with an increase in age-related conditions, including heart disease, decreased bone health, and immune system dysfunction. As an alternative to the risks of hormone replacement, prolonging the lives of ovaries is getting attention. When an old mouse receives a transplanted ovary from a young mouse, her lifespan is expanded. Oviva Therapeutics is testing a hormone in mice and cats that expands ovarian functionality over time. A small randomized clinical trial is testing 5 milligrams of rapamycin weekly versus placebo for three months in women aged thirty-five to forty-five years who have evidence of menopausal transition and fulfill multiple hormone level inclusion criteria. The primary outcome is a measure of ovarian reserve, a surrogate for prolonging ovarian function. It’s in the early phase of testing, but, as Renee Wegrzyn, director of Advanced Research Projects Agency for Health, aptly pointed out, “Ovaries are the only organ in humans that we just accept will fail one day.” That passive acceptance is clearly getting a relook.
We must also turn to our good old friends, dogs. In a randomized trial of a proprietary senolytic with a NAD+ supplement (more on that later) in fifty-nine senior dogs testing low dose, full dose, or placebo, there was modest benefit of owner-reported cognition scores with the full dose. That’s controversial, but while we’re onto dogs, there’s another intervention that could be groundbreaking for the regulatory side of antiaging.
The company is called Loyal Dogs and the proprietary drug (LOY-001) reduces insulin growth factor (IGF-1), which may account, at least in part, for why small breeds of dogs live considerably longer. An injectable given every three months for dogs more than seven years of age and forty pounds reduced IGF-1 levels, and an ongoing placebo-controlled trial is underway in more than one thousand dogs for potential lifespan extension. Loyal Dogs has two other drugs (properties not disclosed) in pill form that will enter large randomized trial testing. While we know nothing about these drugs for efficacy or safety, the key point is that the FDA has given provisional acceptance of a drug for extending lifespan. That’s why the announcement landed on the front page of the New York Times in late 2023.