Nutritional zinc, oxidative stress and immunosenescence: biochemical, genetic and life style implications for healthy ageing

EU project of the 6th Framework STREP

Ancona  FOOD-CT-2003-506850 (2004-2006)

Coordinated by Dr. Eugenio Mocchegiani

A hallmark of cellular ageing is the increase in the oxidatively modified proteins. Oxidative damage in lymphocytes is critical given the importance of the immune system for maintaining good health and for successful ageing. Some antioxidant micronutrients in the diet, such as zinc, control the development and function of the immune cells, the activity of stress-related proteins [metallothioneins, chaperones, ApoJ, PARP-1, NO, MsrA] and antioxidant enzyme (SOD) and help to maintain genomic integrity and stability, thus suggesting diet-gene interactions. During ageing, the intake of zinc decreases due to inadequate diet or/and intestinal malabsorption, thus causing frailty, general disability and increased incidence of age-related degenerative diseases (cancer, infections and atherosclerosis). No focused research has been performed thus far to clarify the intrinsic biochemical mechanisms and the impact of nutrient zinc on the genome during immunosenescence. The applicants will therefore study, the role of zinc in the gene expression and functions of metallothioneins, chaperones, NO, MsrA, ApoJ, telomerase, PARP-1 and DNA-repair as a function of immunosenescence in lymphocytes from old subjects including nonagenarians, as well as in ill old patients affected by age-related diseases and in T-cell clones as in vitro model. Particular attention will be paid to the processing of oxidised proteins by proteasome, which decreases in ageing. The activity of all proteins herein studied is impaired in ageing and this is directly and indirectly controlled by zinc ion bioavailability. The zinc deficiency in the elderly will be evaluated through the screening of polymorphic allele frequency of proteins involved in zinc ion metabolism (such as Hsp70-2 and TNF-alpha) and their relationships to gender. The results will form a rationale for the promotion of healthy ageing through a zinc supplementation and for the development of new zinc-related anti-ageing drugs.