Chapter 9 - Dietary restriction and mTOR and IIS inhibition: the potential to antiaging drug approach

Abstract

The impact of dietary restriction (DR) on disease and aging has received increasing attention in recent years. There is substantial evidence that DR displays many benefits, including reduced inflammation, lowered cardiovascular risk and improved metabolic fitness. In addition, many growing evidence indicates that DR and aging interact through partially overlapping mechanisms in the activation of some conserved nutrient-signaling pathways, mainly the insulin/insulin-like growth factor (IIS) and the mammalian target of Rapamycin (mTOR). Although the involvement of the mTOR pathway and IIS signaling in regulating life span and aging has been studied extensively, the underpinning mechanisms remain elusive. On the other hand, recent discoveries indicate that the aging process can be improve or delay through specific pharmacological approaches. Therefore, this chapter reviews the literature concerning: (i) the emerging insights linking mTOR and IIS signals to various processes related to aging and disease; (ii) recent discoveries on how DR attenuates aging through AMPK and SIRT1 pathways; (iii) discuss the regulatory mechanisms that may delay or improve the aging process from pharmacological discoveries. We also focus on illustrating some potential anti-aging drugs, such as metformin, rapamycin or resveratrol, and verify their actual effects in vivo. In conclusion, systems approaches and polypharmacology to develop anti-aging drugs may be the most effective way to target nutrient-sensing network in improving late-life health.