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Molecular mechanism of caloric restriction mimetics-mediated neuroprotection of age-related neurodegenerative diseases: an emerging therapeutic approach

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Abstract

Aging-induced neurodegenerative diseases (NDs) are significantly increasing health problem worldwide. It has been well documented that oxidative stress is one of the potential causes of aging and age-related NDs. There are no drugs for the treatment of NDs, therefore there is an immediate necessity for the development of strategies/treatments either to prevent or cure age-related NDs. Caloric restriction (CR) and intermittent fasting have been considered as effective strategies in increasing the healthspan and lifespan, but it is difficult to adhere to these routines strictly, which has led to the development of calorie restriction mimetics (CRMs). CRMs are natural compounds that provide similar molecular and biochemical effects of CR, and activate autophagy process. CRMs have been reported to regulate redox signaling by enhancing the antioxidant defense systems through activation of the Nrf2 pathway, and inhibiting ROS generation through attenuation of mitochondrial dysfunction. Moreover, CRMs also regulate redox-sensitive signaling pathways such as the PI3K/Akt and MAPK pathways to promote neuronal cell survival. Here, we discuss the neuroprotective effects of various CRMs at molecular and cellular levels during aging of the brain. The CRMs are envisaged to become a cornerstone of the pharmaceutical arsenal against aging and age-related pathologies.

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Acknowledgements

The authors acknowledge the financial support provided by Amity University Uttar Pradesh, Noida, India. We apologize to all authors whose reports on caloric restriction mimetics could not be covered in this review.

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  1. Amity Institute of Neuropsychology and Neurosciences, Amity University Uttar Pradesh, Noida, 201313, India

    Apoorv Sharma & Abhishek Kumar Singh

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A.S. Literature review, and writing of the original draft; A.S. Prepared figure 1-3; A.K.S. Prepared figures 4-5; A.K.S. Conceptualization, supervision, and final reviewing and editing; All authors reviewed the manuscript

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Sharma, A., Singh, A.K. Molecular mechanism of caloric restriction mimetics-mediated neuroprotection of age-related neurodegenerative diseases: an emerging therapeutic approach. Biogerontology 24, 679–708 (2023). https://doi.org/10.1007/s10522-023-10045-y

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