Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity

Calabrese, Vittorio; Cornelius, Carolin; Cuzzocrea, Salvatore; Iavicoli, Ivo; Rizzarelli, Enrico; Calabrese, Edward J.

doi:10.1016/j.mam.2011.10.007

Cited by 196 publications

(178 citation statements)

References 221 publications

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“…Hormesis is the adaptive response to small harmless doses of a potentially fatal environmental or intrinsic stress stimulus, which renders the organism resistant to increased doses of this particular stressor. The signalling pathways that mediate resistance or adaptation to stress are also involved in longevity and have been already introduced in previous chapters (Calabrese et al, 2011;Johnson et al, 2002;Parsons, 1995). In this part of the review, we highlight autophagy as an integral component of several stress response mechanisms, which represents a conserved stress coping strategy in eukaryotes.…”

Section: Environmental/cellular Stress Signals Induce Autophagy-mediamentioning

confidence: 96%

Autophagy and ageing: Insights from invertebrate model organisms

Lionaki

Markaki

Tavernarakis

2013

Ageing Research Reviews

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a b s t r a c tAgeing in diverse species ranging from yeast to humans is associated with the gradual, lifelong accumulation of molecular and cellular damage. Autophagy, a conserved lysosomal, self-destructive process involved in protein and organelle degradation, plays an essential role in both cellular and whole-animal homeostasis. Accumulating evidence now indicates that autophagic degradation declines with age and this gradual reduction of autophagy might have a causative role in the functional deterioration of biological systems during ageing. Indeed, loss of autophagy gene function significantly influences longevity. Moreover, genetic or pharmacological manipulations that extend lifespan in model organisms often activate autophagy. Interestingly, conserved signalling pathways and environmental factors that regulate ageing, such as the insulin/IGF-1 signalling pathway and oxidative stress response pathways converge on autophagy. In this article, we survey recent findings in invertebrates that contribute to advance our understanding of the molecular links between autophagy and the regulation of ageing. In addition, we consider related mechanisms in other organisms and discuss their similarities and idiosyncratic features in a comparative manner.

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Section: Environmental/cellular Stress Signals Induce Autophagy-mediamentioning

confidence: 96%

Autophagy and ageing: Insights from invertebrate model organisms

Lionaki

Markaki

Tavernarakis

2013

Ageing Research Reviews

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“…Mild cellular stress is known to engage the vitagene network of pro-survival proteins such as heat shock proteins 70 (Hsp70), Hsp32 (also known as heme oxygenase 1), thioredoxin, and sirtuin-1 (8,10,20). In order to examine whether PI also increased vitagenes, we probed for Hsp32, Hsp70, thioredoxin, and sirtuin-1 ( Supplementary Fig.…”

Section: Ape1 Induction Mediates the Neuroprotective Effect Of Pi Andmentioning

confidence: 99%

“…Hormesis is defined as favorable reactions to low-level stress and has been observed in the toxicological literature for many decades (4)(5)(6)(7)47). Hormesis elicits U-shaped or biphasic responses to stress and is mediated, at least in part, by the co-ordinated network of vitagenes (8)(9)(10)20). Preconditioning increases the expression of the vitagenes thioredoxin, sirtuin-1, Hsp32, and Hsp70 (1,2,16,59).…”

Section: Ape1 Preserves Neuronal Structure and Functionmentioning

confidence: 99%

Apurinic/Apyrimidinic Endonuclease 1 Upregulation Reduces Oxidative DNA Damage and Protects Hippocampal Neurons from Ischemic Injury

Leak

Li²,

Zhang³

et al. 2015

Antioxidants & Redox Signaling

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Aims: Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme that participates in base-excision repair of oxidative DNA damage and in the redox activation of transcription factors. We tested the hypothesis that APE1 upregulation protects neuronal structure and function against transient global cerebral ischemia (tGCI). Results: Upregulation of APE1 by low-dose proton irradiation (PI) or by transgene overexpression protected hippocampal CA1 neurons against tGCI-induced cell loss and reduced apurinic/apyrimidinic sites and DNA fragmentation. Conversely, APE1 knockdown attenuated the protection afforded by PI and ischemic preconditioning. APE1 overexpression inhibited the DNA damage response, as evidenced by lower phospho-histone H2A and p53-upregulated modulator of apoptosis levels. APE1 overexpression also partially rescued dendritic spines and attenuated the decrease in field excitatory postsynaptic potentials in hippocampal CA1. Presynaptic and postsynaptic markers were reduced after tGCI, and this effect was blunted in APE1 transgenics. The Morris water maze test revealed that APE1 protected against learning and memory deficits for at least 27 days post-injury. Animals expressing DNA repair-disabled mutant APE1 (D210A) exhibited more DNA damage than wild-type controls and were not protected against tGCI-induced cell loss. Innovation: This is the first study that thoroughly characterizes structural and functional protection against ischemia after APE1 upregulation by measuring synaptic markers, electrophysiological function, and long-term neurological deficits in vivo. Furthermore, disabling the DNA repair activity of APE1 was found to abrogate its protective impact. Conclusion: APE1 upregulation, either endogenously or through transgene overexpression, protects DNA, neuronal structures, synaptic function, and behavioral output from ischemic injury. Antioxid. Redox Signal. 22,[135][136][137][138][139][140][141][142][143][144][145][146][147][148]

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“…A group of genes involved in preserving cellular homeostasis during stress conditions, called vitagenes, and sirtuins, among others, are involved in a wide spectrum of cellular defense [14,87,88]. Indeed, one of the ways by which sirtuins regulate the stress response is through protein stability, which can readily affect the levels of oxidatively modified/damaged proteins [89].…”

Section: Sirtuins In Protein Stability and Cellular Stress Responsementioning

confidence: 99%