Why Do We Lose Cognitive Ability as We Age?
About two-thirds of Americans experience at least some cognitive impairment by the time they reach age 70. In New Hampshire, where the population is the second oldest in the United States, age-related illness is a particularly salient public health issue. However, much remains unknown about how and why brains struggle to retain their full function. Recent research from the 91制片厂 (91制片厂) clarifies part of the aging neuroscience puzzle by revealing that two different types of cognitive abilities 鈥 those developed through lifelong experiences versus those needed to adapt to new information 鈥 are affected differently by age.
Adam Brockett
鈥淎ging is an economic issue as well as a health issue, because the burden of care will be massive as the elderly population increases,鈥 says , assistant professor of biology at the 91制片厂 College of Life Sciences and Agriculture. 鈥淲e need to learn more about how normal, healthy aging affects our neurobiology so that more people have the insights they need to enjoy a high quality of life at age 70 and beyond.鈥
Brockett鈥檚 larger scientific goal is to better understand and inform how lifestyle choices, pharmaceutical options and other measures could help people maintain robust cognitive function as they age. His current research is key to setting an important starting point for understanding how cognitive loss occurs with age 鈥 a first step to finding preventative and therapeutic management tools.
Different kinds of intelligence
Human brains are complex, with different brain regions and neural circuits performing distinct tasks and serving different functions. Do these regions and functions deteriorate in the same way, at the same pace? In a recent paper, published in , Brockett and colleagues show that two different types of cognitive ability exhibit different levels of decline with age.
鈥淩esearch has suggested that what鈥檚 called 鈥榗rystallized intelligence,鈥 a base of information gained with experience throughout life, is well maintained,鈥 says Brockett. 鈥溾楩luid intelligence鈥 involves quickly processing and adapting to new information or changes in circumstance, and that tends to be what is lost over time. In order to stop or delay impairment, you first need to know which neural processes are changing and which are holding steady.鈥
Epigenetic changes: Every cell in your body has the same DNA, which provides the base-line information needed by every organism to develop and live. But how can different types of cells鈥攕uch as nerve cells, immune cells, liver cells, and others鈥攂e so different and perform specialized functions? The answer is, in part, epigenetics.
Epigenetic marks are chemicals that are added or removed from DNA strands or associated proteins to regulate when genes are active or shut down. Consider a massive book with thousands of chapters. If the pages within many chapters are paper clipped, you would only be able to read the pages without the clips. Later, moving some paper clips around wouldn鈥檛 change the text in the book, but would enable you to read the previously inaccessible chapters. In that way, the same book can provide entirely different information at different times, depending on where and when the paper clips are added and removed.
It's long been known that epigenetics play a key role in orchestrating development, in which a single fertilized cell divides and differentiates into the trillions of cells that make up a mature organism. Researchers are now investigating how it contributes to aging. Brockett鈥檚 work with HDAC5 is about epigenetics, as acetyl groups function to activate genes, and deacetylases, such as HDAC5, remove them, suppressing gene activity. Research into which genes are shut down in the brain as we age will reveal important aging mechanisms in the brain and, hopefully, how to counteract them to retain full function for a longer time.
To investigate, Brockett turned to rats, a common model for both aging and behavioral research, in part because of their two-year average lifespans. Collaborating with Matthew Roesch from the University of Maryland, Brockett trained two different groups of animals to perform two cognitive tasks, one designed to test self-control (crystallized intelligence) and the other behavioral adaptation (fluid intelligence), to receive a reward.
They then assessed the two groups 11 months apart, comparing one group鈥檚 performance at 3-4 months and 10-12 months of age and the other group at 14-15 and 21-23 months of age. This allowed the research team to detect differences at four age points, including those in 鈥渕iddle age,鈥 rather than the more standard young versus old comparison.
Their results support earlier research findings that aging does not affect different neural processes in the same way. The rats performed progressively worse with age on the test that demanded rapid behavioral adaptation and fluid intelligence. Performance on the test involving self-control and crystallized intelligence, however, remained consistent.
The researchers also considered the fact that any observable changes in cognitive function likely began far earlier, at the molecular level. They assessed whether the quantities of a certain molecule changed during the aging process and if that may contribute to eventual dysfunction.
鈥淲e looked at HDAC5, a protein called a histone deacetylase, that has been found at high levels in the brains of some people with cognitive impairment,鈥 says Brockett. 鈥淏asically, it works to shut down some genes, and the more of it there is, the less active the genes are. We found that the rats with high levels of HDAC5 did slightly worse on the fluid intelligence test, suggesting that reduced gene activity in brain neurons may play a role in them aging and losing full function.鈥
Beyond age
As his research moves forward, Brockett will take a comprehensive look at the molecular shifts that occur with age and how they contribute to eventual impairment. He doesn鈥檛 expect the culprit to be a single gene or molecular pathway, but instead a wide range of more subtle changes that are part of the natural aging process.
Brockett is particularly interested in the effects of behavioral and environmental factors on brain aging, specifically exercise and nutrition. Regular exercise has been shown to lower the risk of cognitive decline as well as neurodegenerative conditions such as frontotemporal dementia and Alzheimer鈥檚 disease at the population level. The mechanisms have been studied extensively, but researchers still don鈥檛 know exactly how it works.
鈥淗ow does exercise trick the brain into thinking that we鈥檙e not yet 60 at the molecular level even if we might be older in calendar years?鈥 says Brockett. 鈥淥ur rats will spend plenty of time on exercise wheels as we dig into that question.鈥
The research was supported by the National Institute on Drug Abuse grant DA031695.