On September 24, 2020, MBS students had the opportunity to take a deep dive into what leading-edge research has revealed about the influence of lifestyle interventions on age-associated decline and dysfunction. The talk, led by alumnus Girish Harinath MBS’20—a cell biologist/neuroscientist with a Master of Business and Science (MBS) degree in Biotechnology & Genomics—was hosted by fellow MBS alumnus Matt Watson MBS’18, who graduated with a concentration in Urban Environmental Analysis and currently works as an assistant project manager at Arcadis.
To Live is to Stress
Harinath defined stress as any factor (physical, chemical, environmental, or psychological) that elicits a physiological response from our body. Therefore, stress can include anything from the air we breathe, to UV radiation from the sun, to the thoughts flowing through our mind. Stress can be acute or chronic, and can be experienced as either eustress or distress.
Eustress is any stress that induces a positive adaptive response that makes us more resilient. One example is the physical stress of exercise that initially causes damage to muscle which serves to signal an adaptive response that builds the muscle up stronger than before. Distress is any stress that induces a maladaptive response that compromises our health, such as viruses or toxins that make us sick.
For the stress-response paradigm, Harinath explained how the human body, when confronted with a stress stimulus, initiates an acute response that is responsible for defusing the stressor. This could take many forms including a rapid inflammatory response, changes in macronutrient utilization, or activation of “protective” gene networks. After the stressor is mitigated, the system returns to a baseline, called homeostasis, and makes a physiological adaptation to prepare the body for similar stressors that may be encountered in the future. In other words, it’s about building resilience—an ability that is helpful (if not essential) in so many aspects of our lives.
Resilience: Our Ultimate Life Insurance
Three states of the resilience process: baseline state, response state, and adapted state.
Resilience is the process of encountering and adapting well in the face of various forms of stress—from psychological or physical adversity including mental and physical trauma to environmental stressors such as toxins, low oxygen levels, and/or temperature extremes. Adaptations can take the form of changes in gene expression, protein activation, cellular activity, and optimized and/or improved organ functionality that effectively “remove the fangs'' from a given stressor so that it is more easily dealt with in future encounters.
An effective stress response involves considerable physiological changes to the body in an effort to diffuse the stressor, but also a return to baseline once the stressor is eliminated. This encompasses the basic concept of homeostasis, the process of maintaining a relatively stable internal state that is permissive of the billions of chemical reactions taking place in our body every day to keep us alive.
Building resilience is about gradually improving our homeostatic state so that our bodies are better adapted to face future stressors more efficiently and effectively. We can build resilience in a controlled and methodical manner via exposing ourselves to various stressors such as temperature extremes, physical activity, certain plant-derived molecules, and cognitively challenging situations.
The popular term for this concept is called hormesis, which will be discussed in more detail below.
Chronic Stress: A Downward Spiral
Chronic stress is characterized by an unbalanced stress response that persists regardless of the presence of the original stressor. Over time, chronic, sustained stress can adversely affect physical and emotional health and lead to chronic inflammation, which is an energetically demanding and messy internal process.
Because energy is triaged disproportionately towards the site of inflammation, other tissues of the body are neglected. Further, each immune response is accompanied by a marginal amount of inefficiency and “friendly fire.” Ultimately, the persistence of these two processes leads to damage accumulation and accelerated aging. Chronic stress is also associated with increased secretion of cortisol into the bloodstream, which induces metabolic alterations (notably, high levels of blood sugar) that damage brain cells, reduce muscle mass, and further accelerate both cellular damage and the aging process.
When talking about stress and aging, Harinath discussed a concept that he termed “the deadly distractions.” This concept highlights how the cells of our body have access to finite resources, and any imbalance of resource allocation to the various tissues of our body ultimately leads to organismal aging. Within this paradigm, he discussed the idea of “deadly distractions” that hoard energy away from key quality control systems of the body—a process that leads to gradual and insidious damage accumulation within compromised tissues. These distractions include reproductive stress, growth-signaling stress, environmental stress, and inflammatory stress.
The long-term influence of stress can lead to many different forms of damage accumulation that ultimately drive the aging process. While aging has traditionally been regarded as an inevitable process of degeneration and decay, says Harinath, studies from the past three decades have consistently shown that:
- Aging is a malleable process
- Evolution modulates the rate of aging via biochemical knobs
- We can turn these knobs to modulate our longevity
Hormesis: What Doesn’t Kill You Makes You Stronger (or, What Doesn’t Kill You Makes You Live Longer)
Hormesis refers to the process in which exposure to a little bit of stress activates a protective response that leaves the body stronger than before. “We need to learn how to engage with stress to boost our resilience,” said Harinath. “And the concept of hormesis is critical to this understanding.”
There are many types of stimuli that trigger hormetic responses, and each one provides a different kind of resilience within the various tissues of the body. Types of resilience can range from how our body detoxifies chemicals in the environment to how it utilizes energy stores (i.e. body fat), or mounts an inflammatory response. This is why taking a holistic approach and incorporating a wide range of hormetic stressors into our lifestyle is important for healthy aging.
Three examples of hormesis are exercise, temperature, and phytochemicals.
Exercise: The Ultimate Polypill
Exercise is an excellent example of hormesis. During the process of exercise, we push ourselves through discomfort to move our body, exert energy, and stress our cardiovascular system and skeletal muscles. This stress actually creates damage within these tissues and pushes them to the limits of their capacity; however, it is through our bodies’ response to this stress (exercise recovery) that our bodies undergo magnificent adaptations that lead to stronger muscles, more efficient cardiovascular functioning, and better overall fitness. And it doesn’t take much to reap the benefits. It turns out that just a little dose of exercise stress can have profound, system-wide benefits.
Harinath shared a bit of exciting research which suggests that a single ten-minute, high-intensity interval training workout (think: jumping lunges, burpees, and squats, for 20 seconds each) can induce effects in the body—such as increased fat burning and mitochondrial efficiency—that can last up to 36 hours). And these effects aren’t just limited to benefits for our muscles and cardiovascular system: regular workouts can lead to improved brain health, enhanced immune systems, and the cultivation and/or growth of healthy microbiome.
One mechanism that drives these systemic health benefits is through oxygen deprivation. When individuals “lose their breath” for short periods of time during an exercise session, this sends a signal throughout the body that activates the expression of “resiliency genes,” which, in turn, activate systemwide repair and restore programs that clear away damaged proteins, activate stem cells, upregulate mitochondria, and promote the health of multiple organ systems.
Temperature: The Power of Discomfort
Harinath described that intense temperature change could trigger a cascade of positive changes in the body that help cultivate system-wide resilience. Our body produces particular proteins in response to intense cold and/or heat—appropriately named “cold-shock proteins (CSPs)” and “heat-shock proteins (HSPs),” respectively. Interventions such as cryotherapy or cold showers activate CSPs that enhance antioxidant systems and trigger the release of powerful anti-inflammatory molecules. This, in turn, protects against the onset and progression of age-associated chronic inflammation, autoimmune disorders, and some forms of cancer.
Heat exposure from sources such as saunas and hot baths activates expression of HSPs that induce the repair of critical cellular components (such as DNA and proteins), and which stimulate the release of powerful anti-anxiety molecules and cleanse the body of toxic chemicals through sweat. Emerging scientific evidence is showing that this process holds significant promise for prevention and treatment of conditions including psychological disorders, cardiovascular disease, and dementia.
Phytochemicals: Ancient Protectors
Phytochemicals are molecules released by stressed plants that help protect those plants against various environmental stressors (i.e. pathogens, temperature, predators, etc.) by activating cellular rejuvenation and “repair systems” encoded in the plants’ genomes. When humans consume these stressed plants—which include broccoli sprouts, turmeric plant, wine (fermented grapes), blueberries, and kale—the phytochemicals serve the same function within us by activating protective mechanisms encoded within our own respective genomes.
These protective mechanisms include DNA-repair, stem-cell activation, and cellular damage removal to name a few, says Harinath. Further, research shows that people consuming a plant-based diet have decreased heart disease and cancer risk compared with individuals who do not. He explained that certain phytochemicals, such as curcumin, epigallocatechin-3-gallate (EGCG), and quercetin, have been shown to counteract many of the cellular damages that accumulate with aging, and, hence, have significant longevity-enhancing potential. Harinath suggested that there are thousands of phytochemicals found in nature and we can incorporate them into our diet by eating a range of colorful fruits, vegetables, sprouts, and fermented products including wine!
Sleep: The “Swiss Army Knife” of Good Health
Nearly all living organisms on earth, from insects to humans to whales, have at least one thing in common: They all sleep. Humans spend roughly one third of their lives asleep. The human sleep cycle lasts about 90 minutes, and, during that time, our brain sequentially moves through five stages of sleep: The first four stages are non-rapid eye movement (NREM) sleep, and the fifth stage is when rapid eye movement (REM) or “dream sleep” occurs. These cycles repeat over and over for as long as we sleep. For example, if we sleep for six hours (360 minutes), then we would go through four sleep cycles.
Harinath stated that each stage of sleep serves a role in repairing and rejuvenating our body from the damages incurred from our time awake. For this reason, the quality of our sleep is just as important as the quantity of sleep. The different stages of sleep help regulate blood-pressure, improve learning and memory, clear toxic aggregates, and improve overall brain health.
In fact, neuroscientists have found that REM sleep is crucial for dealing with emotional imbalances such as anxiety and depression—effectively serving as an “emotional therapist” of sorts. Harinath stated, “It’s not time that heals all wounds, but adequate REM sleep that heals all wounds.” The all-pervasive influence of sleep penetrates the depths of our organs and tissues right down to the level of individual cells.
Research shows that less than six hours of sleep can have a negative impact on the exact same functions that are maintained and/or improved by adequate amounts of quality sleep, including immune health, cardiovascular fitness, and brain plasticity, says Harinath, who concluded that “optimizing sleep quality is our most effective form of health insurance.”
Regular exercise, bracing for (and enduring) temperature discomfort, following a healthy diet, and ensuring regular, high-quality sleep are essential elements of overall health; by improving these habits—all of which are within our control to improve—we can improve the overall quality of our lives and health, and therefore slow the aging process. Harinath ended this talk by encouraging students to utilize these lifestyle interventions to manage stress and potentially stave off chronic inflammation while at the same time boosting their mental and physical resilience.