Obesity and High-Fat Diets: Accelerating Brain Aging and Cognitive Decline

by Ella

Obesity remains a pressing global public health issue, with its prevalence escalating at an alarming rate. As per the World Health Organization (WHO), 16% of the global population was affected by obesity in 2022. However, the United States grapples with a more pronounced dilemma, with the Centers for Disease Control and Prevention (CDC) reporting a staggering 41.9% obesity rate in 2020. The concern is exacerbated by the rising incidence of obesity among younger demographics, with 160 million children and adolescents worldwide afflicted by this condition in 2022.

The ramifications of obesity extend beyond physical health, with individuals facing an elevated risk of various health complications proportional to the severity of their condition. These health risks encompass cardiovascular ailments, type 2 diabetes, musculoskeletal disorders like osteoarthritis, and certain cancers, including endometrial, breast, and colon cancers.


A Glimpse into Research Findings:

A groundbreaking study, set to be presented at the American Physiology Summit from April 4–7 in Long Beach, CA, and awaiting publication in a peer-reviewed scientific journal, unveils a concerning correlation between obesity and accelerated brain aging, ultimately leading to cognitive decline.


Lead study author, Dr. Sharon Negri, a postdoctoral fellow in the Department of Neurosurgery at the University of Oklahoma Health Sciences Center, elucidates, “Diet-induced obesity triggers a spectrum of systemic inflammatory responses, exerting pervasive effects on the body, including the cerebrovasculature. The primary mechanism through which obesity may induce senescence in the cerebrovasculature is attributed to the chronic inflammatory milieu it instigates.”


Understanding the Mechanisms:

Mounting evidence suggests a detrimental impact of obesity on brain function. Although the precise mechanism remains elusive, inflammation, a hallmark consequence of obesity, is postulated to impede cognitive function.


Dr. Negri elucidates, “Adipose tissue in obese individuals secretes various bioactive molecules, including pro-inflammatory cytokines, capable of disseminating and affecting distant organs, including the brain.” She further elaborates, “These inflammatory mediators contribute to vascular cell senescence, fostering the development of cerebrovascular senescence, consequently impeding vascular regulation and responsiveness to neural stimuli.”

Insights from Animal Studies:

In a recent animal study, researchers explored the effects of obesity and high-fat diets on brain blood vessels in mice and their implications for cognitive function. The study involved feeding novel transgenic mice (p16-3MR mice, which enable visualization and selective elimination of senescent cells) with either a 60% fat diet or a standard 10% fat diet.

The findings unveiled a surge in endothelial cell senescence in the blood vessels of mice subjected to a high-fat diet compared to those on a regular diet. Moreover, mice on the high-fat diet exhibited compromised cognitive function, as evidenced by impaired performance on the radial arm water maze test (RAWM).

Potential Therapeutic Avenues:

To assess the significance of senescent cells, researchers treated older obese mice on a high-fat diet with Navitoclax/ABT263, a compound known for selectively eliminating these cells. Remarkably, following treatment, mice demonstrated improved cognitive function.

Dr. Negri underscores the therapeutic potential of this finding, stating, “Our research, in conjunction with studies by other groups, underscores the substantial reversal or prevention of cognitive decline associated with aging through strategies targeting senescent cells.”

However, she cautions against hasty therapeutic applications, advocating for further research into the molecular mechanisms involved and the safety and efficacy of Navitoclax in human cognitive function.

Upholding Cognitive Health:

In light of these findings, Dr. Negri underscores the pivotal role of weight management in safeguarding cerebrovascular health and cognitive function in later life. “Our primary objective is to unravel the specific contribution of senescent cells to the natural aging process and their interplay with obesity,” she articulates. “Through this focus, we aspire to unearth the fundamental mechanisms underpinning the aging process, culminating in the development of targeted interventions enhancing both physical and cognitive well-being in our twilight years.”

As research endeavors continue to unravel the intricate interplay between obesity, brain aging, and cognitive function, the imperative remains clear: prioritizing weight management and adopting a balanced diet are indispensable tenets in safeguarding cognitive vitality and overall well-being across the lifespan.



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