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Is carbonyl/AGE/RAGE stress a hallmark of the brain aging?

Abstract

Recent studies have linked carbonyl stress to many physiological processes. Increase in the levels of carbonyl compounds, derived from both endogenous and exogenous sources, is believed to accompany normal age-related decline as well as different pathologies. Reactive carbonyl species (RCS) are capable of damaging biomolecules via their involvement in a net of nonspecific reactions. In the advanced stages of RCS metabolism, variety of poorly degraded adducts and crosslinks, collectively named advanced glycoxidation end products (AGEs), arises. They are accumulated in an age-dependent manner in different tissues and organs and can contribute to inflammatory processes. In particular, detrimental effects of the end products are realized via activation of the specific receptor for AGEs (RAGE) and RAGE-dependent inflammatory signaling cascade. Although it is unclear, whether carbonyl stress is causal for age-associated impairments or it results from age- and disease-related cell damages, increased levels of RCS and AGEs are tightly related to inflammaging, and therefore, attenuation of the RAGE signaling is suggested as an effective approach for the treatment of inflammation and age-related disorders. The question raised in this review is whether specific metabolism in the aging brain related to carbonyl/RCS/AGE/RAGE stress.

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Abbreviations

AGEs:

Advanced glycoxidation end products

RAGE:

Receptor for AGEs

RCS:

Reactive carbonyl species

ROS:

Reactive oxygen species

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Acknowledgment

The author gratefully acknowledges three anonymous referees for their helpful suggestions and comments that improved the manuscript.

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This work was supported by the grant from the Ministry of Education and Science of Ukraine (#0118U003477).

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This article is part of the special issue on Aging Brain in Pflügers Archiv—European Journal of Physiology

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Semchyshyn, H. Is carbonyl/AGE/RAGE stress a hallmark of the brain aging?. Pflugers Arch - Eur J Physiol 473, 723–734 (2021). https://doi.org/10.1007/s00424-021-02529-y

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Keywords

  • AGE/RAGE signaling
  • Antiglycation system
  • Neuroinflammation
  • RAGE antagonists
  • Reactive carbonyl and oxygen species