title: Calcium signaling alterations, oxidative stress, and autophagy in aging.
abstract: CONCLUSIONS
  Aging is a multi-factorial process that may be associated with several functional and structural deficits which can evolve into degenerative diseases. In this review, we present data that may depict an expanded view of molecular aging theories, beginning with the idea that reactive oxygen species (ROS) are the major effectors in this process. In addition, we have correlated the importance of autophagy as a neuroprotective mechanism and discussed a link between age-related molecules, Ca(2+) signaling, and oxidative stress.
  
  
  BACKGROUND
  There is evidence suggesting that alterations in Ca(2+) homeostasis, including mitochondrial Ca(2+) overload and alterations in electron transport chain (ETC) complexes, which increase cell vulnerability, are linked to oxidative stress in aging. As much as Ca(2+) signaling is altered in aged cells, excess ROS can be produced due to an ineffective coupling of mitochondrial respiration. Damaged mitochondria might not be removed by the macroautophagic system, which is hampered in aging by lipofuscin accumulation, boosting ROS generation, damaging DNA, and, ultimately, leading to apoptosis.
  
  
  RESULTS
  This process can lead to altered protein expression (such as p53, Sirt1, and IGF-1) and progress to cell death. This cycle can lead to increased cell vulnerability in aging and contribute to an increased susceptibility to degenerative processes.
  
  
  CONCLUSIONS
  A better understanding of Ca(2+) signaling and molecular aging alterations is important for preventing apoptosis in age-related diseases. In addition, caloric restriction, resveratrol and autophagy modulation appear to be predominantly cytoprotective, and further studies of this process are promising in age-related disease therapeutics.
authors: Department of Pharmacology, Federal University of São Paulo , São Paulo, Brazil .
authors: Rodrigo Portes
authors: RP
authors: Ureshino
authors: Katiucha Karolina
authors: KK
authors: Rocha
authors: Guiomar Silva
authors: GS
authors: Lopes
authors: Cláudia
authors: C
authors: Bincoletto
authors: Soraya Soubhi
authors: SS
authors: Smaili
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D020013:Calcium Signaling / Q000235:genetics / Q000502:physiology*; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species