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Review
. 2019 Jul 19;8(7):749.
doi: 10.3390/cells8070749.

Dicarbonyl Stress at the Crossroads of Healthy and Unhealthy Aging

Cecilia Nigro  1   2 , Alessia Leone  1   2 , Francesca Fiory  1   2 , Immacolata Prevenzano  1   2 , Antonella Nicolò  1   2 , Paola Mirra  1   2 , Francesco Beguinot  1   2 , Claudia Miele  3   4
Affiliations
Review

Dicarbonyl Stress at the Crossroads of Healthy and Unhealthy Aging

Cecilia Nigro et al. Cells. .

Abstract

Dicarbonyl stress occurs when dicarbonyl metabolites (i.e., methylglyoxal, glyoxal and 3-deoxyglucosone) accumulate as a consequence of their increased production and/or decreased detoxification. This toxic condition has been associated with metabolic and age-related diseases, both of which are characterized by a pro-inflammatory and pro-oxidant state. Methylglyoxal (MGO) is the most reactive dicarbonyl and the one with the highest endogenous flux. It is the precursor of the major quantitative advanced glycated products (AGEs) in physiological systems, arginine-derived hydroimidazolones, which accumulate in aging and dysfunctional tissues. The aging process is characterized by a decline in the functional properties of cells, tissues and whole organs, starting from the perturbation of crucial cellular processes, including mitochondrial function, proteostasis and stress-scavenging systems. Increasing studies are corroborating the causal relationship between MGO-derived AGEs and age-related tissue dysfunction, unveiling a previously underestimated role of dicarbonyl stress in determining healthy or unhealthy aging. This review summarizes the latest evidence supporting a causal role of dicarbonyl stress in age-related diseases, including diabetes mellitus, cardiovascular disease and neurodegeneration.

Keywords: aging; diabetes mellitus; dicarbonyl stress; glycation; glyoxalase system; hormesis; methylglyoxal; neurodegeneration; obesity; vascular complications.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cellular processes compromised by methylglyoxal (MGO) and aging. MGO accumulation fosters some aging-related molecular events that are schematically reported in the figure. AGE: advanced glycation end products; MGdG: 3’-(2’-deoxyribosyl)-6,7-dihydro-6,7-dihydroxy-6-methylimidazo-[2,3-b]purine-9(8)one; RAGE: advanced glycation end products receptor.
Figure 2
Figure 2
Dicarbonyl stress as determinant of aging quality. MGO accumulation during aging (red color in the arrow) induces tissue damage if not efficiently counteracted by defense mechanisms (e.g. glyoxalase system), leading to metabolic disease, vascular dysfunction, neuronal damage and, thus, unhealthy aging. If a good balance between MGO formation and defense mechanism activity is maintained, this guarantees healthy aging.
See this image and copyright information in PMC

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