The role of macroautophagy in the ageing process, anti-ageing intervention and age-associated diseases.
Macroautophagy is a degradation/recycling system ubiquitous in eukariotic cells, which generates nutrients during fasting under the control of amino acids and hormones, and contributes to the turnover and rejuvenation of cellular components (long-lived proteins, cytomembranes and organelles). Tight coupling between these two functions may be the weak point in cell housekeeping. Ageing denotes a post-maturational deterioration of tissues and organs with the passage of time, due to the progressive accumulation of the misfunctioning cell components because of oxidative damage and an age-dependent decline of turnover rate and housekeeping. Caloric restriction (CR) and lower insulin levels may slow down many age-dependent processes and extend lifespan. Recent evidence is reviewed showing that autophagy is involved in ageing and in the anti-ageing action of anti-ageing calorie restriction: function of autophagy declines during adulthood and is almost negligible at older age; CR prevents the age-dependent decline of autophagic proteolysis and improves the sensitivity of liver cells to stimulation of lysosomal degradation; protection of autophagic proteolysis from the age-related decline co-varies with the duration and level of anti-ageing food restriction like the effects of CR extending lifespan; the pharmacological stimulation of macroautophagy has anti-ageing effects. Besides the involvement in ageing, macroautophagy may have an essential role in the pathogenesis of many age-associated diseases. Higher protein turnover may not fully account for the anti-ageing effects of macroautophagy, and effects of macroautophagy on housekeeping of the cell organelles, antioxidant machinery of cell membranes and transmembrane cell signaling should also be considered.
Bergamini
E
E
Centro di Ricerca di Biologia e Patologia dell'Invecchiamento, University of Pisa, Scuola Medica, via Roma 55, 56126 Pisa, Italy. ebergami@ipg.med.unipi.it
Cavallini
G
G
Donati
A
A
Gori
Z
Z
D000375:Aging / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D031204:Caloric Restriction; D015444:Exercise; D006801:Humans