The biochemistry and cell biology of aging: metabolic regulation through mitochondrial signaling.
Cellular and organ metabolism affects organismal lifespan. Aging is characterized by increased risks for metabolic disorders, with age-associated degenerative diseases exhibiting varying degrees of mitochondrial dysfunction. The traditional view of the role of mitochondria generated reactive oxygen species (ROS) in cellular aging, assumed to be causative and simply detrimental for a long time now, is in need of reassessment. While there is little doubt that high levels of ROS are detrimental, mounting evidence points toward a lifespan extension effect exerted by mild to moderate ROS elevation. Dietary caloric restriction, inhibition of insulin-like growth factor-I signaling, and inhibition of the nutrient-sensing mechanistic target of rapamycin are robust longevity-promoting interventions. All of these appear to elicit mitochondrial retrograde signaling processes (defined as signaling from the mitochondria to the rest of the cell, for example, the mitochondrial unfolded protein response, or UPR(mt)). The effects of mitochondrial retrograde signaling may even spread to other cells/tissues in a noncell autonomous manner by yet unidentified signaling mediators. Multiple recent publications support the notion that an evolutionarily conserved, mitochondria-initiated signaling is central to the genetic and epigenetic regulation of cellular aging and organismal lifespan.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, Singapore; and.
Yun Chau
YC
Long
Theresa May Chin
TM
Tan
Inoue
I
Takao
Bor Luen
BL
Tang
D000375:Aging / Q000378:metabolism*; D000818:Animals; D044127:Epigenesis, Genetic; D006801:Humans; D008136:Longevity; D008659:Metabolic Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D018384:Oxidative Stress; D015398:Signal Transduction
aging; mitochondria; mitochondria retrograde signaling; mitokine; reactive oxygen species