by Steven N. Austad, PhD
AFAR Senior Scientific Director
The past 20 years have seen a wealth of discoveries identifying cellular processes that influence the length of healthy life in animal models. We need to move these discoveries toward developing effective lifestyle, dietary, and pharmacological interventions to enhance and extend our years of health, or healthspan.
The field is ready to target the processes of aging in the same way that we target individual disease processes. Addressing the many maladies of aging one at a time—the traditional medical approach—only extends the period of ill health as one disease replaces another. Targeting aging can preserve health itself.
A major gap exists in the pipeline of translation from animal studies that successfully target aging to implementation of those discoveries in people. AFAR seeks to provide research and training in the technical skills and knowledge necessary to close this gap. Doing so will accelerate the pace at which laboratory discoveries become available as health-prolonging treatments.
How can one test promising interventions that target the biological processes of aging? Pharmaceutical companies have avoided research and development in this area because they have assumed that it would take many decades to convince regulatory bodies such as the FDA that their drugs effectively did what they promised. Researchers with AFAR have shown that this assumption is wrong. They have developed and continue improving clinical trial paradigms to make such trials relatively short and cost-effective. Further work in this area will hasten the passage of health-extending drugs from the laboratory to the home medicine cabinet.
AFAR is planning a large clinical trial to establish proof-of-concept that the condition of aging is a treatable composite of age-related diseases. Known as TAME (Targeting Aging with Metformin), the trial will investigate whether participants who take metformin—a widely used type 2 diabetes drug with a 60-year safety record—experience delayed development or progression of age-related chronic diseases compared with those who take a placebo.
The TAME Trial will seek to convince the U.S. Food and Drug Administration to approve aging itself as an indication for treatment—opening the door to an infusion of needed research and development funding for a range of drugs and compounds that are already in the pipeline.
Among the many promising potential therapies are:
Senolytics, which target so-called “zombie cells” (damaged or senescent cells that tend to accumulate as we age and destroy other cells around them). A combination of the leukemia drug dasatinib and the supplement quercetin, which extended lifespan and healthspan in mice, has moved into human trials.
Rapamycin, which has been shown to extend lifespan in mice by 25 percent and is now the focus of the University of Washington-based Dog Aging Project to see if it promotes longer lifespans in canines.
NAD boosters, molecules that restore levels of nicotinamide adenine dinucleotide, or NAD—a compound found in all living cells that naturally decreases by half as we age.
Humanin, a mitochondria-derived peptide (a short chain of amino acids naturally found in many foods) that prevents age-related cognitive decline in mice and has been associated with improved cognitive age in humans.
Fisetin, a natural product found in many fruits and vegetables, which extends health and lifespan in mice by clearing out senescent cells.
What’s often referred to as “young blood,” or blood from younger animals, which can studies show can rejuvenate the cells and tissues of older animals.
SS-31, a mitochondria-targeted peptide that reverses age-related oxidation reduction (redox) stress and improves tolerance of exercise in aged mice.
The top breakthroughs in aging research today have been driven by AFAR experts.
