POLIMENI Ascanio, MD-Chronogeroprotection: Novel mechanism for old and new molecules
Session: NEW TRENDS IN GEROPROTECTION
Aging is a complex, heterogeneous, and multifactorial phenomenon, which is the consequence of multiple and deep interactions between genes and environment. The positive effects of Caloric Restriction on health and life extension are highly conserved across the vast majority of species, including human subjects. Despite these effects on health, it is highly unlikely that CR will become a realistic or popular life choice for most human subjects given the level of restraint required. Consequently significant research is focusing on identifying compounds that will replicate the benefits of CR without the obligation to adhere to stringent reductions in daily food intake.
In the last years, a number of drugs and nutrients including antioxidants, vitamins, and hormones are widely advertised as geroprotectors. Geroprotectors are therapeutics that affect the root cause of aging and age-related diseases, and thus prolong the life-span of animals. Although these compounds show significant promise, there is a need to properly understand the mechanisms through which these drugs act. Most of geroprotectors such as melatonin, metformin, rapamycin and resveratrol are anti-oxidant or anti-aging molecule regulators. It is usually believed that life-extending capacity of geroprotectors are related to their specific anti-aging mechanisms or to the induction of the hormetic adaptive response mimicking the Caloric Restriction or Chronofasting actions. In the first part of this review are explored the main geroprotective mechanism of actions of the most important old geroprotectors(metformin,resveratrol,berberine) and new ones(spermidine,AICAR and other AMPK activators).
Circadian clocks that comprise clock genes exist throughout the body and control daily physiological events. The central clock that dominates activity rhythms is entrained by light/dark cycles, whereas peripheral clocks regulating local metabolic rhythms are determined by feeding/fasting cycles. Nutrients reset peripheral circadian clocks and the local clock genes control downstream metabolic processes. Metabolic states also affect the clockworks in feedback manners.For unknown reasons, there is a decline in circadian rhythms with age, concomitant with declines in the overall metabolic tissue homeostasis .This disruption of the relationship between the clock and the nutrient-sensing networks might underlie age-related diseases.Resetting the circadian clock leads to well being and increased life span, whereas clock disruption is associated with aging and morbidity so a great scientic interest is focused on molecules that could reset the circadian machinery armony.We know today that CR and TIME RESTRICTION FEEDING or INTERMITTENT/PERIODIC FASTING exert many of their positive effects on aging process through the reset of central and peripheral clocks.Last researches have also proved similar conclusions in the mechanism of actions of old ones and new ones geroprotectors that so could be named Chronogeroprotectors.
Increased longevity and improved health can be achieved by different life style interventions ( cyclical feeding/fasting regimens,scheduled exercises and sleep) and a personalized treatment with Chronogeroprotectors like metformin, polyphenols,polyamines and other AMPK and sirtuins activators that reset circadian rhythms and may lead to better synchrony in metabolism and physiology and also enhance an active Aging.
