POLIMENI Ascanio, MD Friday, October 23, 2015
Targeting AMPK as a novel approach in slowing cardiometabolic risk, aging and aging related diseases
Session: PRACTICAL AGING DRIVER-Chairman: A Polimeni-G Scapagnini
Efficient control of energy metabolic homeostasis, enhanced stress resistance, and qualified cellular housekeeping are the hallmarks of improved healthspan and extended lifespan. AMPK signaling is involved in the regulation of all these characteristics via an integrated signaling network.
Many studies with lower organisms have revealed that increased AMPK activity can extend the lifespan. Experiments in mammals have demonstrated that AMPK controls autophagy through mTOR and ULK1 signaling which augment the quality of cellular housekeeping. Moreover, AMPK-induced stimulation of FoxO/DAF-16, Nrf2/SKN-1, and SIRT1 signaling pathways improves cellular stress resistance. Furthermore, inhibition of NF-kappa b signaling by AMPK suppresses inflammatory responses that is the key factor of aging process(inflammaging).Emerging studies indicate that the responsiveness of AMPK signaling clearly declines with aging.The decreased sensivity of AMPK pathway aging related is mainly promoted by physical inactivity,disnutrition and sarcopenic obesity.
The loss of sensitivity of AMPK activation to cellular stress impairs metabolic regulation, increases oxidative stress and reduces autophagic clearance. These age-related changes activate innate immunity defence, triggering a low-grade inflammation and metabolic disorders.
In this lecture is reviewed in detail the signaling pathways of this integrated network through which AMPK controls energy metabolism, autophagic degradation and stress resistance and ultimately the aging process and the different intervention on this key pathway activation.Safe nutritional strategies like intermittent fasting or caloric restriction and different kind of physical activiy are showed in this lecture.
New studies on CR or Exercise mimetics drugs, nutrients and phytochemicals are also mentioned.
Waiting for conclusive studies on CR-Exercise mimetics drugs and supplements,body composition optimizzation through safe life style choises is suggested with the goal to upregulate AMPK pathway that regulates aging process and its related diseases.
