Cellular Aging Characteristics and Their Association with Age-Related Disorders

Abstract

Different molecular signaling pathways, biological processes, and intercellular communication mechanisms control longevity and are affected during cellular senescence. Recent data have suggested that organelle communication, as well as genomic and metabolic dysfunctions, contribute to this phenomenon. Oxidative stress plays a critical role by inducing structural modifications to biological molecules while affecting their function and catabolism and eventually contributing to the onset of age-related dysfunctions. In this scenario, proteins are not adequately degraded and accumulate in the cell cytoplasm as toxic aggregates, increasing cell senescence progression. In particular, carbonylation, defined as a chemical reaction that covalently and irreversibly modifies proteins with carbonyl groups, is considered to be a significant indicator of protein oxidative stress and aging. Here, we emphasize the role and dysregulation of the molecular pathways controlling cell metabolism and proteostasis, the complexity of the mechanisms that occur during aging, and their association with various age-related disorders. The last segment of the review details current knowledge on protein carbonylation as a biomarker of cellular senescence in the development of diagnostics and therapeutics for age-related dysfunctions.

Endosomal Escape of Polymer‐Coated Silica Nanoparticles in Endothelial Cells

“…This phenomenon was documented to occur physiologically in various eukaryotic systems [20,21] in particular in response to cellular damage and aging. [22,23] Conversely, HNP were found to display an increasingly homogenous distribution that could be resulting from the loss of particle segregation within lysosomal organelles.…”

Reactive oxygen species may influence on the crossroads of stemness, senescence, and carcinogenesis in a cell via the roles of APRO family proteins

“…Consequently, aging may be connected with the accumulation of oxidized molecules categorized by elevated carbonyl residues [32,33]. Enhanced oxidative stress-mediated protein carbonyls may contribute to age-related diseases [34]. Being declined antioxidant defense by aging, fragility to remove oxidative-damaged molecules could probably accelerate the aging further.…”

Protein Carbonylation and Lipid Peroxidation in Hematological Malignancies

“…The main mechanism of protein carbonylation involves the direct action of ROS or the metal-catalyzed oxidation of amino acid side chains, particularly proline, arginine, lysine, and threonine. Carbonyl derivatives can also be generated through the α-amidation pathway or through the oxidation of glutamyl side chains, where the peptide is blocked in N-terminal amino acids by an α-ketoacyl derivative [13]. The indirect mechanism of protein carbonylation involves the carbonylation of lysine, cysteine, and histidine, which may be caused by their reaction with reactive carbonyl groups produced during the oxidation of carbohydrates (e.g., glyoxal (GO), methylglyoxal (MGO)) and lipids (e.g., HNE, MDA or acrolein (ACR)).…”

“…The indirect mechanism of protein carbonylation involves the carbonylation of lysine, cysteine, and histidine, which may be caused by their reaction with reactive carbonyl groups produced during the oxidation of carbohydrates (e.g., glyoxal (GO), methylglyoxal (MGO)) and lipids (e.g., HNE, MDA or acrolein (ACR)). This process of carbonyl generation is termed glycoxidation (the formation of advanced glycation end-products (AGEs)) and lipoxidation (the formation of ALEs), respectively [13][14][15][16][17][18]. Advanced oxidation protein products (AOPPs) are modified structures, similar to AGEs, which also serve as oxidative stress markers [19] (Figure 1).…”