A model for the prevention of neurodegeneration by IIS reduction.

Inhibiting the activity of the IGF-1 receptor by pharmacological agents (I) will hyper-activate the transcription factors, DAF-16/FOXO, HSF-1, and SKN-1/NRF (II). This will lead to elevated expression of the protective gene networks downstream of these transcription factors (III) and to enhanced proteostasis (IV). Functional proteostasis could efficiently disrupt protein aggregates and prevent their accumulation in cells (V). The reduced accumulation of toxic protein aggregates, a prerequisite for the development of neurodegenerative maladies, will prevent the manifestation of these disorders.