Autophagy in aging and in neurodegenerative disorders

Abstract

Autophagy (ATG) is the process of bulk degradation and recycling of long-lived proteins, macromolecular aggregates, and damaged intracellular organelles. Cellular homeostasis requires continuous removal of worn-out components and replacement with newly synthesized ones. Studies in yeast and other mammalian systems have increased our knowledge of the molecular mechanism of autophagy and the role of autophagy in various pathological conditions. Discovery of the genes involved in the process of autophagy has provided insight into the involvement of various molecular pathways. Growing evidence has indicated that diminished autophagic activity may play a pivotal role in the aging process. Cellular aging is characterized by a progressive accumulation of nonfunctional cellular components owing to oxidative damage and a decline in turnover rate and housekeeping mechanisms. Lysosomes are key organelles in the aging process due to their involvement in both macroautophagy and other housekeeping mechanisms. Autophagosomes themselves have limited degrading capacity and rely on fusion with lysosomes. Accumulation of defective mitochondria also appears to be critical in the progression of aging. Inefficient removal of nonfunctional mitochondria by lysosomes constitutes a major issue in the aging process. Autophagy has been associated with a growing number of pathological conditions, including cancer, myopathies, and neurodegenerative disorders. In this review, we discuss the cellular and molecular mechanisms involved in autophagy, the mechanisms of aging, and the possible role of autophagy in this process. Understanding the mechanisms by which autophagy impacts aging may provide useful molecular targets for pharmaceuticals designed to delay aging or correct conditions of premature aging.

Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling

“…44 Recently, NPs are also considered to cause toxic effects through autophagy and lysosomal dysfunction. [45][46][47] Fullerene NPs were shown to induce autophagic vacuolization of HUVECs.…”

Psychological and metabolic stress: A recipe for accelerated cellular aging?

“…Autophagy becomes impaired with aging, and low levels of autophagy are related to cancer and neurodegenerative diseases. 136 Systemic regulators of autophagy are not well studied. However, caloric restriction promotes autophagy, which in turn is required for the caloric restriction-induced longevity in c. elegans.…”

Histopathological and Neurological Features of Atg4b Knockout Mice

“…Mice were housed in a barrier facility at 22 C on a fixed 12-hour light and 12-hour dark cycle and were fed rodent chow #5001 (Purina, St. Louis, MO) ad libitum. Procedures involving animals were conducted in conformity with the Institutional Animal Care and Use Committee guidelines, which are in compliance with the state and federal laws and the standards outlined in the Guide for the Care and Use of Laboratory Animals.…”