Autophagy and aging: new lessons from progeroid mice.
It is widely-assumed that the autophagic activity of living cells decreases with age and probably contributes to the accumulation of damaged macromolecules and organelles during aging. Over the last few years, the study of segmental progeroid syndromes in which certain aspects of aging are manifested precociously or in exacerbated form, has increased our knowledge of the molecular basis of aging. We have recently reported the unexpected finding that distinct progeroid murine models exhibit an extensive basal activation of autophagy instead of the characteristic decline in this process occurring during normal aging. Further studies on Zmpste24-null progeroid mice, which are a reliable model of human Hutchinson-Gilford progeria, have revealed that the observed autophagic increase is associated with a series of metabolic alterations resembling those occurring under calorie restriction or in other situations reported to prolong lifespan. Here, we analyze these unexpected findings and discuss their possible implications for the development of premature aging.
Mariño
Guillermo
G
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
López-Otín
Carlos
C
D000375:Aging / Q000502:physiology*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D011371:Progeria / Q000378:metabolism / Q000503:physiopathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D008666:Metalloendopeptidases; C491250:Zmpste24 protein, mouse