2/14 Brain Functions of Super-Agers

Are you a super-ager? Super-agers are people who are 80 or beyond, who remain mentally sharp, exceeding their peers. There are both physical and sociological traits common to these people. In this lesson, we will take a close look at super-agers, to see how their lifestyle contributes to a long and productive life with a healthy brain. We hope to help identify some things that you can do to become a super-ager.

A super-ager is someone who has maintained their cognitive abilities, even as they have reached the age of 80 and beyond. They would have the memory skills of at least people in their 50s and 60s. They come from many backgrounds and educational levels and have experienced a variety of ups and downs. Some have experienced trauma, such as surviving Holocaust or the death of a child. They seem to have great resilience in the face of stress.

One of the most striking things about these people is the health of their brains. Unlike most older brains which atrophy in time, the age of super-agers can often resemble the brain of people in their 50s or less. In studies comparing the brains of an average 80 year old and an average 50 year old, the older brain will have atrophied (thinned) in the outer layer. However, when comparing the brains of a super-ager to a normal 50 year old, there does not appear to be a difference in the thinning. Even more impressive, when you look at the anterior cingulate (the area of the brain related to attention and memory), it is actually thicker than the average 50 year old brain.

Researchers at Harvard Medical School and Massachusetts General Hospital are currently researching super-agers to see whether there are interventions that can benefit other people. These researchers recognize that as we age, we lose the efficiency of brain regions to communicate with each other, resulting in difficulties in performing cognitive tasks (such as memory, attention and executive function). They have found that with super-agers, memory decline seems to be avoided, along with the brain shrinkage and disruption in communication seen in average older adults. They have also seen that their memories are as strong as young adults.

They have also noted that super-agers are not very common. They consider them to be a rare phenomenon but admit that research is needed. But some of the things that they have discovered, both recently and in past studies include:

· A thicker cortex, not just in a few regions but throughout the cortex: This thickening is seen not only in memory regions but in other functions associated with memory including attention or executive function.

· A larger hippocampus: A larger hippocampus would predict elevated memory abilities. They found that the thicker the cortex, the larger the volume, the better the super-ager was in memory tasks.

· Better connectivity: Unlike typical older adults, they found greater connectivity within the brain. And they found that there was statistically no difference in functional connectivity in their brains when compared to young adults. Their connectivity is more efficient, which would allow more efficient information processing.

· Thicker medial prefrontal cortex: The medial prefrontal cortex is located in the frontal lobes of the brain and seems to be the center of higher cognitive functions. It is thought to contribute to the understanding of morals or values and goal planning. It is also strongly linked to self-referential memory, the type of person someone believes themselves to be. It can be stimulated with activity or social interactions and is increased if there are emotional bonds. Researchers found that this area was thicker in super-agers as compared to other adults, and in many cases was shown to be similar in thickness to young adults.

· Youthful visual cortices: The more recent studies looked at the visual cortex, an important component of memory. This includes neurons involved in processing different categories of images (faces, scenes), requiring a selective function. Learning in a selective way helps create a distinct memory more easily retrieved. This selectivity is called neuronal differentiation, a process that declines with age. So, the group of neurons that would once respond to faces is not activated in response to other stimuli. Their research on super-agers found that their visual cortices maintained youthful patterns, maintaining the same level of differentiation as younger adults. This enables them to create distinct representations more efficiently and a better memory than the typical older adults.

Their future research is looking at the anterior midcingulate cortex. You may recall that super-agers were found to have thicker and larger anterior cortexes than even younger adults. Using a noninvasive brain stimulation which induces neuroplasticity, they are trying to determine whether inducing neuroplasticity will improve the function of this region which should benefit cognition.

Dutch research looked at cognitive functioning of centenarians to determine changes in memory functioning while controlling for other factors. The study used neuropsychological test data and postmortem neuropathological reports from Dutch centenarians who were part of a cohort study. In this study, 330 self-reported healthy centenarians underwent annual visits to researchers to undergo a series of neuropsychological tests which would measure global cognition, memory, executive functions, verbal fluency, visuospatial function and attention/processing speed. After adjusting data for sex, age, education, vision and hearing, the data was used to associate cognitive trajectories underlying cognitive reserve, physical health (at baseline) and Alzheimer’s associated pathology.

From the first testing to the last (all done as centenarians), no decline across cognitive domains were noted except for a slight decline in memory function. Cognitive performance was associated with physical health and cognitive reserve, and none of these were associated with decline. Although there was evidence of the hallmarks of Alzheimer’s in many of the brains, it was not associated with cognitive performance or rate of decline.

Researchers concluded that after up to 4 years, the centenarians maintained high levels of performance despite risk factors of cognitive decline. They concluded that prolonged maintenance of cognitive functioning may be supported by mechanisms underlying resilience against risk factors of cognitive decline. They suggested that resilience may be explained by the build-up of cognitive reserve (having more neural resources available either by genetics or lifetime training). This allows for higher levels of brain damage to accumulate before symptoms of dementia begin. They also found that next to physical health, factors of cognitive reserve such as education, cognitive activities and pre-morbid IQ were associated with cognitive performance.

Among those with longevity genes, is there much impact of lifestyle? This research focused on a cohort of Ashkenazi Jews, descended from a founder population originating in the 15^th century. Most of the group were born in the US or moved before World War 2. These participants were chosen because research from existing studies suggest the genetic contribution to long life in those with exceptional longevity may be greater than the general population. This study was done to see if there were lifestyle factors included in the exceptional longevity.

The study included 477 Ashkenazi Jewish participants who were aged 95 and older. In general, this study population was well educated with almost 75% having completed at least high school.

Some of the factors compared included:

· Body Mass (during lifetime)

· Smoking history

· Alcohol use

· Low calorie diet

· Low fat diet

· Low salt diet

Although it may have seemed obvious that factors such as body mass, alcohol and diet may have influenced the longer life, the study found that people with exceptional longevity were not healthier earlier in life than the general population.

The conclusion of researchers is that those with exceptional longevity may interact with lifestyle and environmental factors differently, but do not seem to adhere to lifestyle choices like smoking, alcohol and special diets.

It did reference past research that suggested children of parents with exceptional longevity were more likely to live longer, had a lower prevalence of cardiovascular disease, hypertension and lipid abnormalities, and that they may be better equipped to handle disease risks faced by the general population. This suggests that the healthy lifestyle choice may counter the disease-associated genes.

Researchers at UCSF have been studying super-agers to determine what it is that allows some older people to thrive. This research goes beyond disease and risk factors, and more towards our individual choices (lifestyle).

Although their approaches to understanding super-agers may vary (self-reported data from large cohorts of people, measuring telomeres, measuring components in the blood of mice), researchers have stumbled on an optimistic conclusion: Decline in memory and other skills are not a normal part of aging.

One factor which may affect our cognition as we age is stress. Researcher Elissa Epel studies participants who are under constant stress (caregivers for example). She looks at the length of individual telomers (caps at the end of chromosomes) which shorten as we age. If telomeres get too short, the cells cannot divide. Tissues cannot be replenished, and risks of chronic diseases increase. Short telomeres in midlife predict an early onset of cardiovascular disease, diabetes, dementia, some cancers and other diseases associated with aging.

Chronic stress can lead to a buildup of proinflammatory factors (called cytokines) which mobilize the immune system to release chemicals that can harm cells. Chronic stress can impair mitochondria (the energy center of cells), accelerate the epigenetic clock (cellular age based on genes) and prematurely shorten the chromosomes’ telomeres.

Epel has found that we can counteract the toxic affects of stress and slow down the aging process. This is done by filtering our view of our life situation to include more gratitude and a mindful response to stress. She has found that caregivers who have more positive emotional connections appear to be protected by the damage caused by stress. Epel believes that biological aging is more under our control than we realize. Small changes (decreasing stress along with meditation, exercise and an anti-inflammatory diet) can reduce and possibly reverse some affects of aging.

This is very new and certainly not a proven method. However, preliminary research is looking at a medication prescribed for prediabetes which may improve your lifespan. The drug is metformin and is currently in phase III of research (typically the final step of research before drug makers can apply for FDA approval). This research stemmed from the observation that people with type 2 diabetes who take metformin have lower death rates from any cause. It also appears to help curb age-related diseases such as heart disease, dementia and Alzheimer’s, and may lower the risk of types of cancer.

Additional research is suggesting that targeting a specific hallmark of aging (telomeres, inflammation, oxidative stress and cell metabolism) may also contribute to an improvement in lifespan. Expect to hear more about this in the future.

We have seen that there are some people who might be born with the right genes. But even so, there are things that we can learn from these super-agers which you can do to live a longer and healthier life. Here are some ideas from research:

· Improve your fitness. Aerobic exercise can enhance your aerobic capacity (oxygen which you can take in and distribute to tissues, also known as VO2 Max). This is something which on average decreases every decade after age 30. Research suggests that those in their 80s who exercised at high intensity for 20 to 45 minutes a day have an aerobic capacity of people 30 years younger. Exercise will also help you to maintain a healthy rate that will decrease your risk of developing dementia. NOTE: Are you curious on how fitness affects your lifespan? Researchers at the Norwegian University has set up a quick survey to help you determine yours. It will only take a few minutes to complete. You can access it here.

· Embrace mental challenges: This is something we discuss often in our class. Research has suggested that by including some healthy mental challenges (calculating income tax, installing computer software, tutoring students, writing poetry etc.) can improve your overall health as well as potentially increase your life span. Remember from our study that the attention region in the brain of super-agers is larger. Research suggests they are also packed with special neurons that might play a role in social processing and awareness.

· Be resilient and allow yourself to be frustrated: This lesson discusses the finding that super-agers are resilient. They use patience and perseverance in their everyday life. You can do this as well. Embrace things that frustrate you (Your smartphone? Editing photos on a new program?) and your may become more resilient to life’s challenges.

· Work with a group: Your social groups are important for a healthy and long life. Use your friends to improve your fitness or to tackle mental challenges.

· Alcohol: Regardless of your views of the healthiness of alcohol, studies with super-agers include many who indulge in a daily drink. This comes with a serious caveat: Moderation. Drinking more than a drink a day is considered a risk factor for dementia.

· Diet: In our section on the studies with super-agers of the Ashkenazi Jews, it was found that these participants did not differ from normal agers in weight, smoking, alcohol use, low fat and non-meat, weight. But a big difference in diet has to do with the diet of these centenarians versus younger people today. These people throughout life included plenty of fresh fruits, vegetables, soups, salads, and healthy dairy, meats and seafood. They avoided packaged foods, but didn’t restrict calories.

· Stress: We did find that stress can play a role in longevity. Managing your stress in any way that you can help you to ward off many of the diseases and illnesses associated with aging.

Although you may not have been born with the good genes, you can practice some of these proven ways to improve your lifespan. At the least, you will be healthy as long as you live, which is more important than just living long.

Beker, e. a. (2021, January 15). Association of Cognitive Function Trajectories in Centenarians With Postmortem Neuropathology, Physical Health, and Other Risk Factors for Cognitive Decline. Retrieved from jamanetwork.com: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2775218

Cassella, C. (2021, July 10). 'Superager' Brains Resist The March of Time to Have Memories Like 25-Year-Olds. Retrieved from sciencealert.com: https://www.sciencealert.com/superagers-with-incredible-memories-have-brains-like-25-year-olds

Collins, S. (2022, February 4). Is There a Cure for Aging? Retrieved from medscape.com: https://www.medscape.com/viewarticle/967916

Piore, A. (2019, Winter). Decoding the Mystery of the Super-Ager. Retrieved from magazine.ucsf.edu: https://magazine.ucsf.edu/decoding-mystery-super-ager

Powell, A. (2022, January 24). Scientists study 'super-aging' minds for clues to possible interventions. Retrieved from medicalxpress.com: https://medicalxpress.com/news/2022-01-scientists-super-aging-minds-clues-interventions.html

Rajpathak, S. e. (2011, August). Lifestyle Factors of People with Exceptional Longevity. Retrieved from ncbi.nlm.nih.gov: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034120/

Rogalski, D. E. (2020, March). What Makes Someone a SuperAger? Retrieved from feinberg.northwestern.edu: https://www.feinberg.northwestern.edu/research/news/podcast/what-makes-someone-a-superager.html

Rogalski, E. (2018, March). 4 Habits of SuperAgers. Retrieved from nm.org: https://www.nm.org/healthbeat/healthy-tips/4-habits-super-agers

Study suggests how 'super aging' older adults retain youthful memory abilities. (2016, September 13). Retrieved from medicalxpress.com: https://medicalxpress.com/news/2016-09-super-aging-older-adults-retain.html

What does it take to be a super-ager? (2017, May 1). Retrieved from health.harvard.edu: https://www.health.harvard.edu/healthy-aging/what-does-it-take-to-be-a-super-ager