Le basi biologiche degli interventi anti-invecchiamento

Ageing (A) is the unavoidable consequence of oxidative and glycoxidative cell-injuries which escaped the action of cell-repair mechanisms. The rate of A is controlled by genetic and environmental factors, including nutrition. Caloric restriction (CR) extends longevity without decreasing ROS generation and may improve function of a cell-repair mechanism sensitive to nutrition: autophagic proteolysis (AP), which is the cell repair mechanism responsible for membrane and organelles maintenance. AP is active in the intervals between feedings to generate oxidizable substrates by the degradation of cell macromolecules and function is physiologically stimulated by CR. It is hypothesized that stimulation of AP is involved in the anti-A action of CR. To support hypothesis it is shown that: function of AP declines with increasing age; age-related decline in AP is prevented by CR, efficacy depending on level and duration like the effect of CR on life-expectancy; function of AP correlates with maintenance of membrane composition; pharmacologic inhibition of AP has pro-A effects; pharmacologic stimulation of AP has anti-A effects. It appears that higher rate of membrane turnover is required to prevent alteration in free-radical metabolism in membranes and accumulation of dolichol, a recently discovered lipophylic antioxidant.