Original article by Anthony L. Komaroff, MD reviewing Davidsohn N et al. Proc Natl Acad Sci U S A 2019 Nov 19
Aging once seemed inscrutable and inevitable. In recent years, however, scientists have identified molecular factors that control aging and have used that information to prolong life in several animal species. Do genes that attenuate aging do anything to protect against “age-related” diseases?
Using a viral vector, investigators introduced three longevity-associated genes into mice and showed that the genes produced their proteins appropriately. This vector-encoded combination gene therapy then was tested in several mouse models of human disease. In mice that develop cardiac hypertrophy and heart failure following aortic constriction, this gene therapy caused heart function to increase by 58%; in mice that develop renal medullary fibrosis and atrophy following ureteral constriction, this gene therapy led to 75% less atrophy. And in an experiment in which mice received a high-fat diet and gained substantial weight, those treated with the combination gene therapy (but not controls that received the viral vector only) had complete reversal of the weight gain and normalization of glucose tolerance, despite continuing high-fat diets. Necropsies revealed no adverse effects of this gene therapy.
Aging is a biological process that can be modified. This study suggests that molecular forces that slow aging might also protect against age-related diseases in mammals. Human studies are unlikely in the near future, but the advancing knowledge about aging biology might ameliorate age-related human diseases someday.