Oxidative stress in aging: advances in proteomic approaches

Abstract

Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual's Quality of Life (QOL). Although extensive research efforts in recent years have been made, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS]), which are currently used as an integral approach to study the aging process. Additionally, the relevance of the oxidative stress factors is discussed. Emphasis is placed on postmitotic tissues, such as neuronal, muscular, and red blood cells, which appear to be those most frequently studied with respect to aging. Additionally, models for the study of aging are discussed in a number of organisms, such as Caenorhabditis elegans, senescence-accelerated probe-8 mice (SAMP8), naked mole-rat (Heterocephalus glaber), and the beagle canine. Proteomic studies in specific tissues and organisms have revealed the extensive involvement of reactive oxygen species (ROS) and oxidative stress in aging.

Figure 1

General stages of the proteomic analysis.

Figure 2

Alteration of proteins by oxidative damage and their turnover. The balance between functional proteins, present in young or healthy organisms, and detrimental or altered proteins, present in a large proportion of aged or diseased organisms, depends mainly on their modification and turnover. If proteins are affected by an increase in oxidative damage or by a low protein turnover, altered proteins accumulate, in contrast to when oxidative damage diminishes and protein turnover increases, when functional proteins increase their proportion and the organism transits to a healthy stage.

Figure 3

Cellular dysfunctions in aging or in age-related diseases by oxidative stress imbalance. (1) Cell metabolism generates reactive oxygen species (ROS) and reactive nitrogen species (RNS), which in turn causes oxidative/nitrosative damage. (2) Proteins are the most affected macromolecules by oxidative stress, undergoing several modifications that avoid their being correctly degraded and recycled by the proteasome, thus generating impaired protein function. (3) Oxidative stress also directly affects cytoskeletal proteins, causing structural damage and signaling alterations. (4) On affecting the mitochondria, oxidative stress alters energy production and (5) on affecting peroxisomes, oxidative stress alters correct metabolic functioning. (6) Oxidative stress also affects the cellular membrane. (7) Finally, all of the previously mentioned affections cause an alteration in the transcriptional activity of the cell, leading to an altered gene expression that in turn leads the cell to the aging process or to degenerative disease.