One unfortunate side effect of aging is loss of brain function. For most people, it starts off here and there with some “forgetfulness” or a modest decline in other thinking skills. But brain loss can be progressive as we age and lead to more problematic conditions such as dementia or Alzheimer’s.
One possible key to maintaining brain functioning and staying sharp-minded could be as simple as living a varied and active life. While this notion isn’t new, current research is validating the benefits of a stimulating environment on the mind by examining the epigenetic mechanisms involved in brain health as we age.
Scientists at the German Center for Neurodegenerative Diseases (DZNE) have reported in Nature Communications a new animal study that indicates how a stimulating environment helps maintain proper functioning of the hippocampus or the brain’s main memory control center. Using mice for their analysis, they looked at what effect environmental enrichment (ENR) had on the epigenetic signature of the brain. What they found was that ENR counteracted aging-induced DNA methylation alterations at genes associated with neuronal plasticity and adult neurogenesis.
An accumulation of errors in the epigenetic machinery is one of the primary hallmarks of aging or key factors causing cellular damage. Prior research has shown that genome-wide DNA methylation changes are highly associated with aging and age-related diseases, such as those involving brain deterioration and neurodegeneration.
Certain lifestyle factors, including physical exercise, cognitive stimulation, and socialization, have been shown to offset age-related brain decreases in humans, allowing for what is called “reserve” or “maintenance” of brain function. Supporting this concept are numerous rodent studies that indicate ENR benefits life-long brain plasticity and health.
In the DZNE study, the scientists tested mice that grew up in two different environments. One group was provided with “enriched” surroundings that included tunnels and toys rearranged periodically. The other was given only basic care in “control” cages. By comparison, it was evident that changes in DNA methylation status were much more pronounced in the control group. The enriched mice had few changes in their epigenetic markings, indicating the achievement of genomic stability.
“We registered so-called methyl groups, which stick to the DNA,” explained DZNE research group leader and author Prof. Dr. Gerd Kempermann. “These chemical attachments do not alter the genetic information per se. Rather, they influence whether individual genes can be activated or not.”
Normally, methyl marks that safeguard the genes relevant for growing new neurons and cellular connections diminish in aging. This was not the case here for the mice that lived in the varied environment. They proved that these methyl marks could be maintained, leading to better brain functioning than their sheltered counterparts in a low-stimulus environment. “Epigenetically, these animals retained a younger hippocampus,” Kempermann said.
While the experiment did not include behavioral testing, the scientists pointed out that it is reasonable to assume that the stabilization of the methylation patterns detected indicates mental fitness in the mice. In fact, several studies done over the years have shown that mice nurtured in a high-stimulus setting perform better on cognitive and retention tests than those raised in low-stimulus environments.
How all these animal studies translate into similar results for humans is questionable, as our reactions to external stimuli are more complex. Still, the basic epigenetic principles apply to humans as well as mice.
More research is needed to further our understanding of the molecular effects of aging in the brain. The good news is epigenetic factors, as we now know, are not necessarily permanent — meaning we may be able to slow down, possibly even reverse, age-related brain dysfunction either through lifestyle changes or potential therapies.
Source: Zocher, S. et al. (2021). Environmental enrichment preserves a young DNA methylation landscape in the aged mouse hippocampus. Nature Communications.
Reference: How Environmental Factors Could Provide for a Young Brain, DZNE – German Center for Neurodegenerative Diseases. June 29, 2021.
