Poor Diet and Lack of Exercise Correlate with Risk of Cognitive Decline and Dementia
It is not surprising to find data showing that a poor diet and lack of exercise correlated with an increased risk of later neurodegeneration and dementia. Plenty of studies exist to note that correlation. The question is the degree to which it is correlation versus causation. There are good reasons to believe that regular exercise slows the onset of neurodegeneration, quite clear mechanistic links that are demonstrated to be causal in animal studies. Equally, a poor diet and lack of exercise correlate with many other potential contributing factors in human populations, not least of which is frailty and other manifestations of aging. So to what degree do these correlations in human data reflect protective effects versus the tendency of those who are most affected by aging, and therefore most likely to decline more rapidly, to eat poorly and exercise little?
New research has found that both diet and exercise can influence the risk of cognitive decline (CD) and dementia by potentially influencing hippocampal neurogenesis long before their onset. The investigation studied how the blood of participants with and without CD and dementia could influence hippocampal neurogenesis in laboratory settings and whether diet and exercise were important factors. Specifically, blood samples of 418 French adults over the age of 65 were collected 12-years prior to CD and dementia diagnosis and tested on human hippocampal stem cells. Additionally, information on each participant's sociodemographic, lifestyle, and clinical data were collected and incidence cognition status and dementia were measured every 2 to 3 years over a 12-year period.
Over the course of the study, the researchers established that 12 years prior to diagnosis, both CD and Alzheimer's were associated with levels of neural stem cell death. The team also found that exercise, nutrition, vitamin D levels, carotenoid and lipid levels are all associated with the rate at which cells die off. Furthermore, physical activity and nutrition were key factors that then also determined CD status. Specifically, researchers found that reduced physical activity and increased malnutrition both increased cell death which in turn increased the risk for future CD.
While previous studies have established that diet and exercise have some protective effects against CD and dementia, these roles have been poorly understood at the neurobiological level. To date, studies on animals have shown how diet and exercise can directly influence hippocampal neurogenesis, potentially explaining how exercise and diet may biologically exert their effects, but this study sheds further light on this in the context of a human model. "If an individual displays an increase in their levels of cell death during differentiation (when neural stem cells are becoming neurons), we can look at this as a potential warning sign of CD. Conversely, a decrease in levels of cell death during proliferation (the process by which a single cell divides into a pair) and reduced hippocampal progenitor cell integrity could be viewed as a predictor for Alzheimer's disease and vascular dementia, respectively."
https://www.pnas.org/content/118/35/e2025647118
Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer
During the aging process, senescent cells secrete inflammatory factors, causing various age-related pathologies. Thus, controlling the senescence-associated secretory phenotype (SASP) can tremendously benefit human health. Although SASP seems to be induced by the alteration of chromosomal organization, its underlying mechanism remains unclear. Here, it has been revealed that noncoding RNA (ncRNA) transcribed from pericentromeric repetitive elements impairs the DNA binding of CCCTC-binding factor, resulting in the alteration of chromosomal accessibility and the activation of SASP-like inflammatory genes. Notably, the ncRNA was transferred into surrounding cells via small extracellular vesicles, acting as a tumorigenic SASP factor. Our study highlights a novel mechanism regulating chromatin interaction and inflammatory gene expression in senescence and cancer.
https://www.nature.com/articles/s42255-021-00438-z
dentifying secreted mediators that drive the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in ageing or Alzheimer's disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the benefits of exercise on cognitive function. Genetic deletion of Fndc5/irisin (global Fndc5 knock-out (KO) mice; F5KO) impairs cognitive function in exercise, ageing and AD. Diminished pattern separation in F5KO mice can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KO mice, adult-born neurons in the dentate gyrus are morphologically, transcriptionally and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral delivery of irisin via adeno-associated viral overexpression in the liver results in enrichment of central irisin and is sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of the cognitive benefits of exercise and is a potential therapeutic agent for treating cognitive disorders including AD.