title: Reprogramming of energy metabolism as a driver of aging.
abstract: Aging is characterized by progressive loss of cellular function and integrity. It has been thought to be driven by stochastic molecular damage. However, genetic and environmental maneuvers enhancing mitochondrial function or inhibiting glycolysis extend lifespan and promote healthy aging in many species. In post-fertile Caenorhabditis elegans, a progressive decline in phosphoenolpyruvate carboxykinase with age, and a reciprocal increase in pyruvate kinase shunt energy metabolism from oxidative metabolism to anaerobic glycolysis. This reduces the efficiency and total of energy generation. As a result, energy-dependent physical activity and other cellular functions decrease due to unmatched energy demand and supply. In return, decrease in physical activity accelerates this metabolic shift, forming a vicious cycle. This metabolic event is a determinant of aging, and is retarded by caloric restriction to counteract aging. In this review, we summarize these and other evidence supporting the idea that metabolic reprogramming is a driver of aging. We also suggest strategies to test this hypothesis.
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.|Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Hanson
authors.affiliation: Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.|Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.|Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Berger
authors.affiliation: Institute of Biology and Soil Sciences of Far Eastern Brach of Russian Academy of Science, Vladivostok, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Trubitsyn
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans
keywords: Gerotarget; aging; energy metabolism; glycolysis; mitochondria; physical activity