Zinc, metallothioneins, and longevity--effect of zinc supplementation: zincage study.
Aging is an inevitable biological process that is associated with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. Because nutritional factors are involved in improving immune functions, metabolic harmony, and antioxidant defense, some nutritional factors, such as zinc, may modify susceptibility to disease and promote healthy aging. In vitro (human lymphocytes exposed to endotoxins) and in vivo (old or young mice fed with low zinc dietary intake) studies revealed that zinc is important for immune efficiency (innate and adaptive), antioxidant activity (supeoxide dismutase), and cell differentiation via clusterin/apolipoprotein J. Intracellular zinc homeostasis is regulated by metallothioneins (MT) via ion release through the reduction of thiol groups in the MT molecule. This process is crucial in aging because high MT levels are not able to release zinc, resulting in low intracellular free ion availability for biological functions. Improvement in these functions occurs in the elderly after physiological zinc supplementation. In this study, the selection of elderly subjects for zinc supplementation is discussed in relation to the genetic background of MT and pro-inflammatory cytokines, such as interleukin-6, because the latter is involved both in MT-gene expression and in intracellular zinc homeostasis.
Immunology Center (Section: Nutrigenomic and Immunosenescence), Research Department, Italian National Research Center on Ageing, Ancona, Italy. e.mocchegiani@inrca.it
Eugenio
E
Mocchegiani
Robertina
R
Giacconi
Catia
C
Cipriano
Laura
L
Costarelli
Elisa
E
Muti
Silvia
S
Tesei
Cinzia
C
Giuli
Roberta
R
Papa
Fiorella
F
Marcellini
Erminia
E
Mariani
Lothar
L
Rink
George
G
Herbein
Audrey
A
Varin
Tamas
T
Fulop
Daniela
D
Monti
Jolanta
J
Jajte
George
G
Dedoussis
Efstathios S
ES
Gonos
Ioannis P
IP
Trougakos
Marco
M
Malavolta
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D051152:Clusterin / Q000276:immunology / Q000378:metabolism; D019587:Dietary Supplements; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008136:Longevity / Q000187:drug effects* / Q000502:physiology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013482:Superoxide Dismutase / Q000378:metabolism; D015032:Zinc / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*
D000975:Antioxidants; D051152:Clusterin; C508600:IL6 protein, human; D015850:Interleukin-6; D008668:Metallothionein; D013482:Superoxide Dismutase; D015032:Zinc