Time in a bottle?

Life extension gets real

Longevity research is gaining momentum, but how soon can you expect to see something in your medicine cabinet that might turn back time? Surprisingly, a few prospects are already generating a buzz. Some of these anti-aging contenders are drugs that have already been approved for treating medical conditions such as diabetes, Parkinson’s or Huntington’s disease, or to combat organ rejection. And as Christopher Scott, PhD, and Laura DeFrancesco, PhD, point out in a recent feature in Nature Biotechnology, nearly all influence cell energetics — the pathways involved in metabolism, insulin signaling and response to metabolic stress or genetic damage. Here are a few attracting the attention of researchers worldwide:

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Rapamycin This compound was first isolated from bacteria discovered in the soil of Easter Island, and is now the darling of the kidney transplant world. In that capacity, it functions to tamp down a patient’s immune response to a foreign tissue. But it also boosts immune response in other situations, like when older people are vaccinated against influenza. Most intriguingly, it increases the life span of organisms ranging from budding yeast to fruit flies to roundworms to our mammalian laboratory buddy, the mouse. It functions by inhibiting a protein called mTOR, which serves as a kind of molecular funnel, gathering diverse data about amino acid and nutrient levels. The downside? Rapamycin treatment comes with a variety of fairly nasty side effects, such as low platelet levels, anemia and elevated cholesterol, that would likely limit any long-term use.

Metformin This widely prescribed oral drug for treating type-2 diabetes works by lowering blood sugar levels, which it accomplishes by increasing insulin sensitivity and suppressing glucose production by the liver. Diabetics receiving the drug appear to have a slightly reduced rate of developing a variety of tumors, and laboratory mice experience a small uptick in longevity.

Resveratrol This naturally occurring substance has made headlines over the past nine years as a potential anti-aging compound present in small amounts in red wine. It functions to increase the expression of a class of proteins called sirtuins, which have been shown to influence longevity in yeast, worms, flies and mice. Sirtuins are highly conserved among species, and appear to be involved in nutrient sensing. Calorie restriction has also been shown to increase sirtuin levels and lead to lower levels of IGF-1 (a hormone with a structure similar to insulin) and blood glucose in humans. Although a clinical trial testing the effect of resveratrol in humans has recently been suspended, another testing a similar molecule called SRT3205 is ongoing.

Young blood This last item is one you’re unlikely to ever store in your medicine cabinet (one would hope!). But researchers including Stanford professors of neurology Thomas Rando, MD, PhD, and Tony Wyss-Coray, PhD, have shown that infusing the blood of young mice into old mice can rejuvenate muscles, activate neuron growth and improve memory and learning in the older animals. Researchers are now trying to identify the components in the blood that provide these benefits (oxytocin, the hormone that stimulates labor in pregnant women and appears to play a role in social bonding, is an intriguing contender). In the meantime, however, a clinical trial was launched in September 2014 by Alkahest (a Menlo Park-based company founded by Wyss-Coray) to test whether regular infusions of blood from donors under the age of 30 can help people recently diagnosed with Alzheimer’s stave off memory loss and reduce other disease-related symptoms.

Krista Conger is a science writer for the medical school's Office of Communication & Public Affairs. Email her at kristac@stanford.edu.

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