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Metallothioneins, ageing and cellular senescence: a future therapeutic target

Eugenio Mocchegiani1, Laura Costarelli, Andrea Basso

  • 1Trans. Res. Ctr. of Nutrition and Ageing, IRCCS-INRCA, Via Birarelli 8, 60121, Ancona, Italy. e.mocchegiani@inrca.it

Current Pharmaceutical Design
|October 16, 2012
PubMed

Insights

Metallothioneins (MT) protect against DNA damage and cellular senescence by releasing zinc ions. Dysfunction in this process contributes to aging and cancer, highlighting MT as a therapeutic target.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Aging research

Background:

  • Oxidative stress and inflammation in aging cause molecular damage, leading to altered gene expression and cellular dysfunction.
  • The antioxidant system, including DNA repair mechanisms, is vital for preventing cellular damage and neoplastic transformation.
  • Cellular senescence, a response to DNA damage, involves cell cycle arrest and the release of factors (senescence-associated secretory phenotype - SASP) that can impair tissue regeneration and promote cancer if clearance is delayed.

Purpose of the Study:

  • To investigate the role of zinc-bound Metallothioneins (MT) in preventing DNA damage and modulating cellular senescence.
  • To explore the connection between MT dysfunction, zinc ion release, and the senescence-associated secretory phenotype (SASP).
  • To assess the potential of MT as a therapeutic target for managing dysfunctional senescent cells.

Main Methods:

  • The study focuses on the known functions of MT as antioxidant proteins and zinc ion donors.
  • It examines the observed reduction in MT expression and intracellular zinc in senescent cells.
  • The research considers the implications of zinc ion release from MT in modulating SASP and cellular senescence.

Main Results:

  • Reduced MT expression and intracellular zinc levels are observed in senescent cells.
  • Dysfunctional zinc release from MT, particularly in chronic inflammation and aging, may contribute to the onset of cellular senescence.
  • Zinc ions released by MT appear to be involved in modulating the senescence-associated secretory phenotype (SASP).

Conclusions:

  • Metallothioneins (MT) play a crucial role in cellular defense against DNA damage and senescence through their antioxidant properties and zinc ion release.
  • Impaired MT function and zinc dysregulation are implicated in aging and the accumulation of senescent cells.
  • MT represent a potential therapeutic target for mitigating the negative effects of dysfunctional senescent cells.

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