As the saying goes, life is a journey, not a destination, and if you are lucky it should be a long, salubrious and enjoyable journey however, living a long life doesn’t always guarantee that the quality of said long life is going to be stellar. And while longevity and quality are not mutually exclusive, understanding the science of longevity (or epigenetic aging) can be crucial when looking to optimize, thrive (and not just survive) and enjoy your time here on this earth (1).

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What is Longevity?

The goal with aging is not to evade it, but rather enrich the process and possibly mitigate some age-related pathologies that can come with living longer.  Longevity can be defined as the length or duration of one’s lifetime or what we refer to as “life expectancy.” According to the CDC, the average life expectancy for Americans has actually slightly declined, with the expected lifespan of someone born in the US to be 76.4 years now.  Life expectancy at birth for women in the United States dropped 0.8 years from 79.9 years in 2020 to 79.1 in 2021, while life expectancy for men dropped one full year, from 74.2 years in 2020 to 73.2 in 2021 (National Center for Health Statistics, 2022) (2).

Despite the many advances in modern medicine, we are beginning to see more and more age-related diseases associated with aging, such as Alzheimer’s disease (AD), cardiovascular disease (CVD), osteoporosis, diabetes, and general sensory, psychological, and cognitive changes. Yet despite the slight dip in life expectancy, by the year 2050, the American 85-year-old and overpopulation will triple, which means we need to figure out a way to increase, improve and enhance the overall quality of life. Targeting key molecular mechanisms that underlie the biology of healthy aging can be a novel first step toward ameliorating longevity (3, 4).

Biomarkers of Aging

There is now newer research that shows that the rate of aging can differ between individuals, with our biological age differing from chronological age and how this impacts our longevity. Biological aging may be a better indicator of how we can enhance longevity, which can be assessed through various biomarkers of aging (which will be discussed below) (5).

In the journal Aging Cell, the study uses biomarker data collected from the blood samples of almost 5,000 participants in the Long Life Family Study, and researchers actually generated 26 different predictive biomarker signatures (6).

These biomarkers assess the function of the body’s organs at a cellular level and can include Hemoglobin A1C levels, Homocysteine, Insulin-Like Growth Factor, total cholesterol, Vitamin D levels, and various inflammatory markers such as C-Reactive Protein levels, interleukins, chemokines, and cytokines (7, 8).

Telomere length and Sirtuin genes (also known as longevity or vitality genes) such as SIRT1 to SIRT7, as well as AMPK and mTOR, have also been shown to play a role in the aging process, specifically in the biological aging process. Sirtuins act as epigenetic regulators, which means they can essentially influence how our genes are expressed and control DNA repair (9, 10).

What is Cognitive Decline?

Since our brain can change with age, our cognitive functions may also experience some of these changes, leading to cognitive decline, or what I like to refer to as some-timers moments (sometimes you start to forget things more frequently than before). Cognitive decline is when a person begins to experience a slight and noticeable decline in one's mental abilities, such as thinking, memory recall, judgment, and language. These changes are often recognized by others before we can identify them ourselves and generally, they are not extreme enough to negatively impact our daily life and activities, but certainly noticeable enough to raise concern among loved ones. Learning new information may be a slower process, recalling old information may become more arduous and frequent, misplacing things, becoming more easily distracted,  losing your train of thought, having trouble following conversations, and generally forgetting things more often than you can remember them can all be signs of cognitive decline (11).

The Link Between Cognitive Decline and Age

Brain volume declines with age at a rate of around 5% per decade after age 40, with the actual rate of decline increasing with age, particularly over age 70, and while there is no single cause of cognitive decline, symptoms may be multifactorial. These factors can include changes to proteins in the brain (such as accumulation of beta-amyloid plaque and tau tangles), decreased size and blood flow to the hippocampus (the part of the brain that deals with memory), increased systemic inflammation and brain inflammation, shrinking of the grey matter (where a large number of neurons live that controls movement, memory, and emotions) and neuronal cell death (12, 13).

Nutrition’s Role in Cognitive Decline

A synapse is the point of communication between two neurons. Proper synapse formations depend on adequate nutrient absorption. When synapses lose their communication ability, they die, and the brain begins to shrink. As more neurons die throughout the brain, a person can start showing symptoms of cognitive decline.

Functional Medicine Labs That Are Important to Longevity and Cognition

There are several functional medicine labs that can be integral in your quest for maximizing longevity.

The TruAge Complete Collection is a great jumping-off point for getting a comprehensive look at markers of aging. Biomarkers include average telomere length, immune cell deconvolution, and extrinsic and intrinsic biological age.

The Neural Zoomer Plus Test looks at autoimmune markers and antigens involved in blood-brain barrier disruption, brain autoimmunity, and brain inflammation.

The Alzheimer’s LINX investigates Alzheimer's-associated immune reactivity and can be useful for those individuals who are at a greater risk of developing neurological disorders or looking to identify the early stages of the neurodegenerative process.

How to Prevent Cognitive Decline and Protect Longevity

In order to protect longevity, we need to look at the process of aging, which can include biological, cognitive, and psychological factors, as well as epigenetic factors (such as your diet, lifestyle, and environment) that result in chemical changes to our DNA sequence. It is important to note that aging is a process that comes with gradual changes in our body systems, our cells, and our DNA sequences, which means we can take a preventative approach toward these gradual changes.

Research in the longevity field also shows that molecular integrity (supporting overall health from a cellular level), mitochondrial health, efficient intercellular communication, and the regenerative capacity in tissues are all linked to youthful states (14).

Cultivating a robust lifespan and preserving longevity should also include dietary and lifestyle interventions such as:

Creating an Exercise routine

Research shows that physical activity can support brain health, particularly by improving overall cognitive functions such as problem-solving, emotional balance, thinking, and learning. In fact, one study found that cognitive decline is nearly twice as common among adults who are inactive compared to those who were active. The goal should be to aim for 15- minutes of moderate-intensity physical activity each week, which can be broken up, however you see fit (pun intended). This can look like dancing, walking, playing pickleball, lifting weights, swimming, biking, pilates, or really any movement that you enjoy! Motion is the lotion, which means just keep moving! Exercise has been shown to improve BDNF levels, a key molecule involved in neuroplasticity, which is related to learning and memory (15).

Focusing on Nutrition

There are currently two scientifically researched diets, The MIND diet and KetoFLEX 12/3, that show significant benefits in slowing synapse loss and decreasing cognitive decline.

Getting Key Nutrients

There are certain nutraceuticals that have been studied for their role in overall brain health, which include Vitamin D3, Omega 3 fatty acids, CO-Q10, and B Vitamins.

Since the brain has a rich lipid content and requires high energy demand, is extremely susceptible to free radicals and ROS damage as it has a weak antioxidant capacity. Upon persistent inflammation and increased ROS levels, tissue antioxidant defense mechanisms can become ineffective, making the brain an easy target of excessive oxidative damage, therefore increasing nutrients to counter oxidative damage can be beneficial for overall brain health and longevity (16).

B vitamins are essential nutrients involved in numerous metabolic processes. B vitamins are required for nervous system function, mood and stress support, cognitive health, and neurotransmitter synthesis. B vitamins are important for preventing brain atrophy, which is a result of oxidative damage and stress, and are required for the synthesis and maintenance of myelin, which protects the nerves and brain (17).

The brain is sensitive to inflammation and oxidative damage, which can negatively impact overall cognitive functioning. When levels of omega 3-fatty acids become lower in the brain, increased neuroinflammation can occur, which can cause signaling damage between nerves (18). Mitochondria dysfunction, coupled with oxidative damage, can lead to the death of brain cells and the progression of diseases, such as Alzheimer’s. CoQ10 may reduce the production of ROS and other damaging compounds that have been linked to cognitive decline (19).

Vitamin D receptors are found in brain tissues and Vitamin D has been found to have neuroprotective effects via clearing amyloid plaques, reducing inflammation, and regulating genes that are important for brain function, such as ASPM, a gene that makes a protein that is required for making new neurons in the brain (20, 21).

Mitigate Oxidative Stress & Brain Inflammation

Oxidative stress can activate a variety of pathways that involve the inflammatory process.  When inflammation is triggered by oxidative stress, it can cause imbalances in neural pathways leading to brain inflammation and cognitive decline. The relationship between inflammation, oxidative stress, and cognitive health may be explained due to the presence of free radicals and reactive oxygen species (ROS), both byproducts of the inflammatory process and natural metabolic function. Imbalances and impairment of antioxidant enzyme function due to free radical damage lead to glutathione depletion and increases oxidative stress. This simultaneously can lead to imbalances in glutamate and calcium, as well as mitochondrial dysfunction, causing biochemical distress in the brain. All of this can disrupt neurocircuitry.

The accumulation of ROS can trigger a variety of molecular cascades that increase blood-brain barrier permeability, alter brain morphology, and can thus cause neuroinflammation and neuronal death. ROS generated in brain tissues can negatively impact synaptic communication between neurons which results in neuroinflammation and cell death.

Over time the compounding accumulation of oxidative stress can lead to lower intracellular antioxidant levels and free radical damage, which can further deplete the body of various nutrients, vitamins, and minerals required for healthy brains, including zinc, magnesium, B vitamins, and vitamin C (22, 23).

Lifestyle Changes That Affect Cognition

While it might be tempting to try and biohack your way into a long and full life, adopting some core health principles is going to have greater significance on your overall quality of life. Many of the basic, foundational, and fundamental aspects of overall health should be integrated into a longevity plan. This includes getting sufficient sleep, learning new things, modulating stress, and cultivating meaningful relationships all play a vital role in amplifying longevity.

Summary

Experiencing a long, prolific, and jovial life truly is a gift not guaranteed to everyone therefore focusing on ways to support longevity should be a health non-negotiable.  Enhancing our biological aging capabilities may be a better indicator of how we can better augment longevity, which can be assessed through various biomarkers of aging and functional lab tests. There are also several dietary and lifestyle interventions that can contribute to longevity and cognitive health such as mitigating oxidative stress, increasing the consumption of key brain nutrients, and adopting an exercise routine.