Abstract
Proteins of the GADD45 family play an essential role in the integration of cellular response to a wide variety of stressors and maintenance of homeostasis at the level of a cell, a tissue and an organism. The basic homeostatic processes are implicated in the determination of the progression of aging and development of major age-related disorders. Moreover, GADD45s mediate several well-known aging-associated signaling pathways through the interaction with such proteins as FOXO, p53, ATM, ATR, SIRT1, mTOR and some other. These reasons point out the role of the GADD45 proteins in the aging and life span regulation. Indeed, we have shown that constitutive and conditional (mifepristone-inducible) D-GADD45 overexpression in Drosophila melanogaster nervous system extends median and maximum life span, and increases the resistance to genotoxic, oxidative, thermal stress, and starvation. The life span-extending effect was apparently due to more efficient recognition and repair of DNA damage, because the spontaneous DNA damage in the larva neuroblasts with D-GADD45 overexpression was reduced. However, data obtained for flies with conditional ubiquitous D-GADD45 overexpression demonstrates a negative effect of this intervention on the life span and stress resistance.
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