A special issue of Science Magazine on aging.

You can see titles and abstracts of articles here. And, I want to pass on a section of one of the articles, “Healthy aging: The ultimate preventative medicine,” that lists interventions to delay aging that seem promising.

Abstract: Age is the greatest risk factor for nearly every major cause of mortality in developed nations. Despite this, most biomedical research focuses on individual disease processes without much consideration for the relationships between aging and disease. Recent discoveries in the field of geroscience, which aims to explain biological mechanisms of aging, have provided insights into molecular processes that underlie biological aging and, perhaps more importantly, potential interventions to delay aging and promote healthy longevity. Here we describe some of these advances, along with efforts to move geroscience from the bench to the clinic. We also propose that greater emphasis should be placed on research into basic aging processes, because interventions that slow aging will have a greater effect on quality of life compared with disease-specific approaches.  

Geroscience interventions with translational potential.

Dietary restriction: Dietary restriction (DR) is the most studied intervention for delaying aging. Although not universally effective, a majority of studies have documented significant increases in both life span and health span when DR is applied in laboratory models, including nonhuman primates. Limited studies also indicate important health benefits, including reversal of disease risk factors, in people who practice DR. Although DR is not a viable translational approach at the population level, research in this area has incited the search for alternative dietary modifications (e.g., low-protein diets) or small-molecule DR mimetics (e.g., mTOR inhibitors, see below) that can provide the health benefits of DR without requiring reduced food consumption.

Exercise: A large body of literature provides evidence that the health benefits of exercise are consistent with the enhancement of health span. However, poor compliance, especially in the elderly population, makes this intervention challenging to apply. Thus, there is high interest in developing pharmacologic interventions that would synergize with lower levels of exercise.

mTOR inhibitors: Rapamycin extends life span and promotes health span in mice, as well as in simpler organisms. Treatment beginning late in life is sufficient to extend life span, reverse cardiac decline, and improve immune function in mice. A recent study also reported that a rapamycin derivative significantly boosts immune function in elderly people .

Metformin and acarbose: Metformin and acarbose are widely used antidiabetes drugs. Metformin improves health span in mice and may slightly extend life span, whereas acarbose markedly extends life span in male mice and modestly extends life span in female mice. In a nonrandomized retrospective analysis, diabetic patients taking metformin have reduced mortality compared with diabetic patients not receiving metformin, and they may live longer than nondiabetics not receiving metformin.

NAD precursors and sirtuin activators: Nicotinamide adenine dinucleotide (NAD) precursors such as nicotinamide riboside and nicotinamide mononucleotide have been reported to improve health span in mouse models of muscle aging and cognitive decline. The mechanism of action is not clear, but it may involve activation of sirtuin NAD-dependent protein deacetylases, along with enhanced mitochondrial function. Other, possibly more specific, sirtuin activators also improve health span and slightly extend life span in mice.

Modifiers of senescence and telomere dysfunction:Senescent cells accumulate during aging and secrete factors that promote inflammation and cancer. Telomere dysfunction is a major cause of cell senescence, and strategies to enhance telomerase function offer promise for improving health span, although the possibility of increased cancer risk must be addressed. Likewise, genetic and pharmacological strategies to target and kill senescent cells enhance both life span and markers of health in short-lived mice with high levels of senescent cells.

Hormonal and circulating factors: Age-related changes in important hormones (including sex-steroids, growth hormone, and insulin-like growth factor 1) are well documented; however, the risks and benefits of hormone supplementation in aging remain largely controversial.  Heterochronic parabiosis experiments in which the circulatory system of an aged mouse is shared with that of a young mouse suggest that additional, more subtle humoral factors affect age-associated declines in several tissues, including the brain, muscle, liver, and heart. Some progress has been made toward defining these factors, and an effort is under way to determine whether transfusion of young plasma can delay Alzheimer’s disease.

Mitochondrial-targeted therapeutics: Mitochondrial dysfunction is a major contributor to aging and age-related diseases, although the mechanisms are more complex than initially suggested by the Harman’s free radical theory of aging. Attention is now being directed to interventions that augment mitochondrial function, energetics, and biogenesis, including mitochondrial-targeted antioxidants and NAD precursors.