No two people age the same way. Some become stereotypically absent-minded while others remain just as cognitively sharp as their younger counterparts. Shaping these differences in behavior is a complicated interplay between genes and lifestyle.
A growing body of research is teasing out the relative roles of genetics and lifestyle factors in cognition in old age. In a new paper in Trends in Cognitive Sciences, Goran Papenberg of the Aging Research Center at the Karolinska Institute and Stockholm University in Sweden and colleagues discussed studies of the effects of well-established genes on brain and behavior across the entire adult lifespan or at least several age cohorts.
While the number of available studies is still limited, they support the idea that genes play a bigger role in cognition, and brain structure and function as we age – part of the “resource-modulation hypothesis.” At the same time, lifestyle choices, such as diet and exercise, can moderate the gene-related effects.
Papenberg spoke with CNS about the hypothesis, what the literature says about genetics and lifestyle, and some key takeaways for us all as we age.
CNS: What is the resource-modulation hypothesis?
Papenberg: The resource-modulation hypothesis posits that effects of common genetic variations on brain and cognition may become stronger in old age, contributing to between-person differences. The hypothesis assumes that the relationship between brain resources and cognition is non-linear. Brain resources denote the structural and neurochemical properties of the brain. In older age, brain resources are lowered due to aging-related declines in brain integrity. In young age, brain resources are high and differences in cognition between individuals with different genotypes are smaller or not detectable.
In old age, the same genotype differences become stronger because small differences in brain resources result in larger differences in cognition. So, young individuals carrying disadvantageous genotypes may not differ so much from young individuals carrying more beneficial genotypes. With aging, however, individuals with disadvantageous genotypes of different genes show stronger declines than those individuals with a more beneficial genotype.
CNS: What was the major goal of your new paper?
Papenberg: Our major goal was to describe the increasing evidence that supports the resource-modulation hypothesis. At the same time, we try to highlight some questions that need to be addressed and tested in future studies.
So far, we do not really understand the mechanisms behind the magnification of genetic effects with aging. The question is whether lower brain resources per se lead to increased genetic effects in old age. Alternatively, the stronger genetic effects could be mediated through lifestyle factors that may influence the expression of a gene.
CNS: What types of lifestyle factors?
Papenberg: Leading a physically active lifestyle is probably one of the most powerful lifestyle factors that may counteract the negative effects of a particular genotype in old age. Physical activity affects the body through many different pathways, which makes it a very broad intervention. Of course, with other beneficial lifestyle choices (e.g., nutrition), the beneficial effects of physical activity may even be enhanced.
CNS: What were you most excited to find?
Papenberg: It was exciting to see that the patterns of stronger genetic effects in older age seem to generalize across different genes, behavioral measures, and indicators of brain integrity. Of course, it is rewarding to see that findings of other research groups resemble data we have seen in previous studies, at a time when there was not much evidence in favor of the resource-modulation hypothesis.
CNS: What is an example of a disadvantageous genotype that is more influential in old age?
Papenberg: The APOE genotype e4 is associated with an increased risk for dementia and cognitive decline, for instance with respect to memory. One study showed that the e4 genotype only affected learning and memory after the age of 40, while younger adults carrying the risk genotype did not differ from non-carriers. Similarly, studies have shown that e4 also affects brain functioning and brain integrity stronger in older age.
The interesting part, however, is that our lifestyles seem to modulate the effects of APOE. Disadvantageous lifestyle choices may intensify and advantageous lifestyle choices may counteract the negative effects of APOE e4 in old age.
CNS: What is the general significance of your findings?
Papenberg: There is strong genetic influence on how we age in terms of brain and cognition. It’s important to remember that the effects of single genes are small, but the additive effects of many genes and gene-gene interactions account for a large portion of inter-individual differences. One important take home message, however, is that our lifestyle may intensify or counteract negative genetic effects in old age.
CNS: What’s next for this line of work?
Papenberg: We need to understand the epigenetic mechanisms behind the genetic effects and how these play out with aging. For instance, how do external or environmental factors influence gene expression? It is conceivable that individuals with more advantageous genetic predispositions may actively seek a more stimulating environment. Environmental exposure may, in turn, enhance expression of a particular gene via epigenetic mechanisms, thereby increasing inter-individual differences with aging.
-Lisa M.P. Munoz
