Abstract
Aging is a biological process determined by multiple cellular mechanisms, such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication, that ultimately concur in the functional decline of the individual. The evidence that the old population is steadily increasing and will triplicate in the next 50 years, together with the fact the elderlies are more prone to develop pathologies such as cancer, diabetes, and degenerative disorders, stimulates an important effort in finding specific countermeasures. Calorie restriction (CR) has been demonstrated to modulate nutrient sensing mechanisms, inducing a better metabolic profile, enhanced stress resistance, reduced oxidative stress, and improved inflammatory response. Therefore, CR and CR-mimetics have been suggested as powerful means to slow aging and extend healthy life-span in experimental models and humans. Taking into consideration the difficulties and ethical issues in performing aging research and testing anti-aging interventions in humans, researchers initially need to work with experimental models. The present review reports the major experimental models utilized in the study of CR and CR-mimetics, highlighting their application in the laboratory routine, and their translation to human research.
Highlights
The rapid growth of the world’s aging population has motivated a large effort in the investigation of the mechanisms underlying aging, and in the search of possible countermeasures.Aging is characterized by two connected aspects: the malfunctioning of multiple basic biological processes and the parallel functional decline of the individual
The alteration of the molecular mechanisms regulating basic processes can increase the risk of developing chronic diseases, the functional decline of the individual contributes to a negative outcome to health-challenging situations
The present review aims at providing an overview of the major experimental models utilized in aging research, highlighting the characteristics that allow their use in the study of Calorie restriction (CR) and CR mimetics, and their translation to human research, with a daily-laboratory routine perspective
Summary
The rapid growth of the world’s aging population (https://population.un.org/wpp/; reporting the World population prospect of 2019, accessed on March 2021) has motivated a large effort in the investigation of the mechanisms underlying aging, and in the search of possible countermeasures. Data from different experimental models have largely demonstrated that the mutations that induce life-span extension are associated with an altered activity of the above-listed signaling pathways [3]. Studies performed on experimental models allowed to attribute the life prolongation effects to the modulation of the IGF-1 [9,10], TOR [11], and AMPK signaling pathways [12], and to other targets, such as the above mentioned FOXO that stimulates protein synthesis, NfkappaB, which is involved in the inflammatory response, and Nfr that is implicated in mitochondrial biogenesis [2,13,14,15]. The present review aims at providing an overview of the major experimental models utilized in aging research, highlighting the characteristics that allow their use in the study of CR and CR mimetics, and their translation to human research, with a daily-laboratory routine perspective
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