Autophagy is a fundamental intracellular catabolic process used by cells to degrade and recycle components through lysosomes to balance their sources of energy and building blocks in effort to maintain cellular homeostasis, differentiation, development and survival upon stress. It involves the sequestration and transport of macromolecules and subcellular elements such as nucleic acids, proteins, lipids, and organelles to lysosomes for subsequent degradation. A major regulatory incident in autophagy instigation is exerted by the initiation complex interactions with the nutrientsensing mTOR kinase, and the energy-sensing AMP-activated protein kinase (AMPK), both of which are recognized inducers of autophagy in response to stress. Thus, autophagy initiation is controlled by both nutrient-and energy-sensing mechanisms. A growing body of evidence indicates that autophagy activity deteriorates with age in various organisms. Upon aging and neurodegeneration, flaws in certain steps of autophagy regulation have been observed, which result in accumulation of damaged organelles and protein aggregates. They are harmful for cell metabolism and homeostasis, which further worsens imperfect autophagy. Noteworthy, activation of autophagy has been reported to increase mouse lifespan 207 , and even enhance immune response to vaccination in older individuals by defeating immunosenescence. Autophagy is in a close correlation with numerous other hallmarks of aging, and is currently considered as an integrative aging feature. It is critical for maintaining protein homeostasis (proteostasis). Autophagy work together with the ubiquitin proteasome system to destroy toxic proteins. Upon aging, post-mitotic cells exhibit compromised proteostasis, which correlates with the functional decay of protein quality control tools, including autophagy. Autophagy plays a well-documented role in eliminating dysfunctional mitochondria, termed mitophagy. It has been also demonstrated that autophagy controls cellular senescence, the process of steady proliferation suppression of mitotic cells initiated by diverse stresses, including telomere attrition, DNA impairment, mitochondrial dysfunction, and abnormal hyperproliferative stimuli. Altogether, loss of autophagy generates various cellular malfunctions that exacerbate aging. Since reduced autophagy is implicated in multiple age-related diseases, including neurodegeneration, sarcopenia and osteoarthritis, therapeutic autophagy upregulation has potential towards treating such age-related disorders.