Aging reduces homeostasis and contributes to increasing the risk of brain diseases and death. Some of the principal characteristics are chronic and low-grade inflammation, a general increase in the secretion of proinflammatory cytokines, and inflammatory markers. Aging-related diseases include focal ischemic stroke and neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Flavonoids are the most common class of polyphenols and are abundantly found in plant-based foods and beverages. A small group of individual flavonoid molecules (e.g., quercetin, epigallocatechin-3-gallate, and myricetin) has been used to explore the anti-inflammatory effect in vitro studies and in animal models of focal ischemic stroke and AD and PD, and the results show that these molecules reduce the activated neuroglia and several proinflammatory cytokines, and also, inactivate inflammation and inflammasome-related transcription factors. However, the evidence from human studies has been limited. In this review article, we highlight the evidence that individual natural molecules can modulate neuroinflammation in diverse studies from in vitro to animal models to clinical studies of focal ischemic stroke and AD and PD, and we discuss future areas of research that can help researchers to develop new therapeutic agents.

The anti-aging protein α-Klotho has several therapeutic effects on different pathophysiological conditions, mainly its anti-inflammatory and antioxidant effects. Experimental evidence and observational studies suggest that there are several strategies to increase α-Klotho in the brain and enhance its beneficial effects, thus contributing to improving its neuroprotective and neuroplasticity mechanisms in brain aging, Alzheimer’s, Parkinson’s, and ischemic stroke diseases. In this article, we summarize the relevant information on α-Klotho, brain aging, Alzheimer’s, Parkinson’s, and ischemic stroke diseases and analyze the role of α-Klotho in each of these alterations, as well as the effect of physical exercise, exogenous application of α-klotho, and various drugs approved for different human diseases on α-Klotho production.