Physical Activity,  Human Evolution and Alzheimer's

early man

Physical activity may have played a central role in the evolution of human longevity 2 million years ago. Evidence for physical activity’s role comes from its ability to reduce Alzheimer’s risk in patients who are genetically predisposed to the disease.

Even before the advent of modern medicine, humans have enjoyed longer lifespans than other mammals. The human lifespan began increasing approximately 2 million years ago. However, at this point in human evolution the human genome was homozygous for the allele ɛ4 of the apolipoprotein E (APOE) gene. APOE is a plasma protein involved in cholesterol transport and myelin integrity. Today, the ɛ4 allele is found in the genomes of 14% of the population. The ɛ4 allele is the greatest genetic risk factor for Alzheimers disease and has been implicated in a range of other age-related diseases including cardiovascular disease. The link between APOE ɛ4 and Alzheimers was discovered by renowned geneticist Dr. Vance, currently a professor at the University of Miami. In fact, 40-65% of patients with Alzheimer’s disease carry one or two copies of the ɛ4 allele. Thus, as human lifespans were increasing 2 million years ago, the APOE ɛ4 allele would have posed a significant genetic constraint on the aging population. That is where physical activity comes into play.

Physical activity mitigates the deleterious effects of APOE ɛ4. Researchers in a article published this month in the journal Trends in Neuroscience proposed that physical activity played a critical role in human evolution (Exercise, APOE genotype, and the evolution of the human lifespan, 2014. Raichlen DA and Alexander GE). Human longevity, they argue, came about as our distant ancestors shifted toward higher physical activity levels, reducing the disease risks of being an ɛ4 carrier. Furthermore, current lifespan constraints may reveal an incongruence between our evolutionary history and the lack of physical activity in today’s lifestyles.

APOE ɛ4 carriers develop amyloid plaques in the brain, which is a characteristic cause of Alzheimers. This is because the ɛ4 variant of APOE is not as efficient at catalyzing the breakdown of the peptide beta-amyloid.  Beta-amyloid protein build up is what leads to amyloid plaques. In addition, APOE ɛ4 carriers often have negative age-related physiological and morphological changes in the brain such as reduced hippocampal volume (known as hippocampal atrophy).

Recent studies have demonstrated the role of physical activity in protecting APOE ɛ4 carriers from Alzheimers disease. A study published in Frontiers in Aging Neuroscience found that physical activity negates hippocampal atrophy in aged persons who carry an APOE ɛ4 allele (Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer's disease, 2014. Smith JC, et al.). In this study, the researchers used MRI to calculate hippocampal volume in elderly adults at baseline and then 18 months later. The participants were broken into 4 groups based on whether or not they were carriers of APOE ɛ4 and their physical activity level. Those who carried the APOE ɛ4 allele were labeled high risk for Alzheimers disease. As expected, those who did not carry the APOE ɛ4 allele saw little change in hippocampal volume, regardless of physical activity level. However, participants who carried the APOE ɛ4 allele and reported little physical activity saw a 3% decline in hippocampal volume. The surprising result is that participants who carried the APOE ɛ4 allele, but reported high levels of physical activity, saw no significant decrease in total hippocampal volume. This suggests that physical activity negates hippocampal atrophy caused by the APOE ɛ4 allele. The results are in the figure below.

Both of the articles discussed in this post highlight the importance that physical activity plays in maintaining human health. Furthermore, it reminds us that we evolved as a physically active species. The process of evolution is not fast enough to allow us to adapt to the sedentary lifestyle that has come about over the last century. A previous post in this blog also discussed exercise’s role in reducing Alzheimer’s risk by clearing reactive oxygen species. Apparently, exercise is a good means of preventing Alzheimer’s disease regardless of your genetic make-up.

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