Abstract
Autophagy is a major cellular recycling process that delivers cellular material and entire organelles to lysosomes for degradation, in a selective or non-selective manner. This process is essential for the maintenance of cellular energy levels, components, and metabolites, as well as the elimination of cellular molecular damage, thereby playing an important role in numerous cellular activities. An important function of autophagy is to enable survival under starvation conditions and other stresses. The majority of factors implicated in aging are modifiable through the process of autophagy, including the accumulation of oxidative damage and loss of proteostasis, genomic instability and epigenetic alteration. These primary causes of damage could lead to mitochondrial dysfunction, deregulation of nutrient sensing pathways and cellular senescence, finally causing a variety of aging phenotypes. Remarkably, advances in the biology of aging have revealed that aging is a malleable process: a mild decrease in signaling through nutrient-sensing pathways can improve health and extend lifespan in all model organisms tested. Consequently, autophagy is implicated in both aging and age-related disease. Enhancement of the autophagy process is a common characteristic of all principal, evolutionary conserved anti-aging interventions, including dietary restriction, as well as inhibition of target of rapamycin (TOR) and insulin/IGF-1 signaling (IIS). As an emerging and critical process in aging, this review will highlight how autophagy can be modulated for health improvement.
Highlights
THE NEW BIOLOGY AND HALLMARKS OF AGINGAging is characterized by progressive deterioration of tissues and organs, leading to loss of physiological function and increased risk of death
Autophagy is a major cellular recycling process that delivers cellular material and entire organelles to lysosomes for degradation, in a selective or non-selective manner
In this review we focus on the autophagy process, whose upregulation is a common denominator of all major prolongevity interventions (Hansen et al, 2018), including dietary restriction and mild down-regulation of the nutrient-sensing pathways – insulin (IIS) and mechanistic target-of-rapamycin signalling (Lopez-Otin et al, 2013)
Summary
Aging is characterized by progressive deterioration of tissues and organs, leading to loss of physiological function and increased risk of death. The hope is that such strategies will at the same time prevent agerelated diseases (Niccoli and Partridge, 2012; Kennedy et al, 2014; Partridge et al, 2018) Examples of this approach include the antidiabetic and the anti-aging drug metformin, which is the first drug to be tested for improvement of various health parameters in elderly people (Barzilai et al, 2016), and rapamycin, which has been shown to improve the efficacy of the flu vaccination in aged individuals (Mannick et al, 2018). We explore the potential therapeutic role of autophagy modulation in preventing the aging process and age-related diseases
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