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Review
. 2024 Oct 16;44(1):67.
doi: 10.1007/s10571-024-01493-2.

Clinical Insights on Caloric Restriction Mimetics for Mitigating Brain Aging and Related Neurodegeneration

Anchal Trisal  1 , Abhishek Kumar Singh  2
Affiliations
Review

Clinical Insights on Caloric Restriction Mimetics for Mitigating Brain Aging and Related Neurodegeneration

Anchal Trisal et al. Cell Mol Neurobiol. .

Abstract

Aging, an inevitable physiological process leading to a progressive decline in bodily functions, has been an abundantly researched domain with studies attempting to slow it down and reduce its debilitating effects. Investigations into the cellular and molecular pathways associated with aging have allowed the formulation of therapeutic strategies. Of these, caloric restriction (CR) has been implicated for its role in promoting healthy aging by modulating key molecular targets like Insulin/IGF-1, mTOR, and sirtuins. However, CR requires dedication and commitment to a strict regimen which poses a difficulty in maintaining consistency. To maneuver around cumbersome diets, Caloric Restriction Mimetics (CRMs) have emerged as promising alternatives by mimicking the beneficial effects of CR. This review elucidates the molecular foundations enabling CRMs like rapamycin, metformin, resveratrol, spermidine, and many more to function as suitable anti-aging molecules. Moreover, it explores clinical trials (retrieved from the clinicaltrials.gov database) aimed at demonstrating the efficacy of CRMs as effective candidates against age-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

Keywords: Aging; Alzheimer’s disease; CR-mimetics; Caloric restriction; Clinical trials; Parkinson’s disease.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
An illustration highlighting the effect of normal diet vs. caloric restriction on major nutrient sensing pathways; mTOR, Insulin/IGF-1, and Sirtuins
Fig. 2
Fig. 2
An illustration elucidating the downstream molecular players in nutrient sensing pathways, their cellular effects, and their regulation by Caloric Restriction Mimetics
Fig. 3
Fig. 3
A schematic diagram depicting the methodology and findings of the CALERIE study
Fig. 4
Fig. 4
A diagram depicting the alleviation of AD and PD-associated pathophysiological features upon CRM administration
Fig. 5
Fig. 5
A pie chart depicting the percentage of clinical trials conducted on each CRM
See this image and copyright information in PMC

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