Autophagy and aging: lessons from progeria models.
Autophagy is an evolutionarily conserved process essential for cellular homeostasis and organismal viability. In fact, this pathway is one of the major protein degradation mechanisms in eukaryotic cells. It has been repeatedly reported that the autophagic activity of living cells decreases with age, probably contributing to the accumulation of damaged macromolecules and organelles during aging. Moreover, autophagy modulation in different model organisms has yielded very promising results suggesting that the maintenance of a proper autophagic activity contributes to extend longevity. On the other hand, recent findings have shown that distinct premature-aging murine models exhibit an extensive basal activation of autophagy instead of the characteristic decline in this process occurring during normal aging. This unexpected autophagic increase in progeroid models is usually associated with a series of metabolic alterations resembling those occurring under calorie restriction or in other situations reported to prolong life-span. In this chapter, we will discuss the current knowledge on the relationship between the autophagy pathway and aging with a special emphasis on the unexpected and novel link between premature aging and autophagy up-regulation.
Mariño
Guillermo
G
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, 33006 Spain.
Fernández
Alvaro F
AF
López-Otín
Carlos
C
D000375:Aging / Q000502:physiology*; D000818:Animals; D001343:Autophagy; D004195:Disease Models, Animal; D006801:Humans; D011371:Progeria / Q000503:physiopathology*; D015398:Signal Transduction