Staying healthy is incredibly important in this day and age. While a mutating virus is currently captivating audiences around the world, chronic disease is killing infinitely more people day in and day out.

That’s not to say one is more important than the other. I imagine you don’t care what tries to kill you moreso than putting off death from all causes as long as you can. This is why it’s important to take a more global look at health.

We often look at health as the absence of disease. However, a better definition of health is a state that resists disease. It’s foolish to believe we have no level of control over our health, and that disease takes us at random.

Instead, our behaviors day in and day out build physiology that protects us from disease, both infectious and chronic. Furthermore, when exposed to infectious disease or injury, the health we’ve built prior plays a fundamental role in shaping the outcome. Healthier people tend to heal better.

Of course, aging plays an oversized role in these outcomes, which is why our risk of succumbing to disease increases as we age. A new paper looks at the physiological factors that promote health as defined by resistance to disease.

Today we briefly cover this fantastic paper, which I urge you to read in its entirety because it contains so much more information. (It also has a lot of excellent infographics. This paper is incredibly insightful for many reasons.

First, it gives us awareness of how our body operates under health and pathological conditions. Second, it also gives us some targets to aim for in our goal of staying healthy.

Interestingly, the 2 main topics of this blog are featured prominently in these 8 hallmarks of health. We’re talking about gut health and circadian rhythms.

The 8 hallmarks of staying healthy

The hallmarks of health outlined in this paper are divided into 3 separate categories. These 3 categories are spatial compartmentalization, maintenance of homeostasis, and resistance to stress.

Spatial compartmentalization

It’s important for areas within our body in direct contact with the external environment to prevent foreign bodies from entering the body. Furthermore, in the case of injury or infection, it’s important to sequester the damage and inflammation to prevent systemic problems.

This is concept, called spatial compartmentalization, is the first category in staying healthy.

Integrity of barriers

One aspect of spatial compartmentalization involves maintenance of the integrity of barriers. These barriers keep infectious agents out of our internal environment. This includes maintenance of the gut, blood-brain barrier, skin, and the air-blood barrier in the lungs.

Our cells also contain barriers such as the plasma membrane, mitochondrial membrane, and nuclear membrane. When barriers are breached, inflammation, cell death, and organ dysfunction occur at the organ and cellular level.

If you’ve followed this blog for any appreciable amount of time, you know that we believe barrier integrity is a key component of staying healthy.

Containment of perturbations

When injury or infection occur, it’s important to make sure that it and the immune response stays local in both space and time. We don’t want the infection or injury to set off a systemic response, or to disseminate throughout the body. We also want it to resolve in a timely manner.

There are mechanisms in place to do this. In space, there are both mucus membranes and lymph nodes meant to trap pathogens before they enter the circulation. In time, we have the transition from pro-inflammatory to anti-inflammatory cytokines that resolves infection and inflammation.

Both are essential for preventing chronic damage from persistent and systemic inflammation.

Maintenance of homeostasis

Homeostasis is our tendency to maintain steady internal conditions that promote health. For example, our blood pressure, blood glucose, body temperature, pH, and fluid balance are all maintained within narrow limits.

When any of these factors moves outside of normal limits, our health and function decline. For example, when we are sick, our core body temperature increases to fight the infection. It can also increase blood pressure and glucose levels.

If we play sports during this time, our performance suffers. Once we are over our cold, core body temperature and these other functions return to normal and function improves. Chronic diseases such as hypertension and Type 2 diabetes impair our ability to maintain homeostasis.

Our ability to maintain homeostasis is crucial for our health. The central nervous system uses neurotransmitters as a rapid response to re-establish homeostasis. The endocrine system on the other hand, uses hormones as a slower, more longer term response.

Cell recycling and turnover

Everyday, our cells go through periods of use repair regulated by circadian rhythms. These periods help keep our cells in tip-top shape and make sure they are prepared for the next day’s stressors.

The proteins that make up our cells such as mitochondria, along with the DNA in our nuclues, become damaged. Autophagy is a process by which these proteins are recycled for other purposes. Additionally, this process inactivates and recycles components of enzymes that may compete with one another.

For example, catabolic processes utilize oxidaton while anabolic processes use reduction, which conflict with one another. They utilize the same coenzymes, but work in opposite directions. To make sure growth and repair create healthy cells, they have to be segregated.

Unfortunately, sometimes cells are damaged beyond repair and undergo programmed cell death called apoptosis. Alternatively, replicating cells such as stem cells undergo a process called senescence which causes them to stop replicating. Both processes are crucial for preventing Cancer.

Integration of circuits

There is a synergy between cells within an organ as well as between organs within different systems that promotes health. Within organs, cytokines and other cell signaling molecules allow cells to communicate with one another and carry out the functions of that organ.

Furthermore, hormones, neurotransmitters, and various other proteins allow organ systems with a common goal to cooperate. You’ve likely heard of the gut-brain axis, gut-liver axis, and so on. Integration of organs that play a role in different processes is crucial for health.

For example, the gut, liver, pancreas, kidneys, adrenals, muscle, and fat all play a role in regulating our blood glucose levels. For blood glucose levels to stay in a healthy range, these organs and tissues must properly communicate with one another using various hormones and proteins.

When these circuits break down, or they are unable to properly communicate with one another, we experience pathology. In the above example, Type 2 diabetes is the major pathology we experience when this circuit becomes dysfunctional

Rhythmic oscillations

Consistent environmental exposures lead to the development of anticipatory physiological responses. This generates rhythms of hormones, metabolites, and immune responses that help us navigate our environment successfully.

There are several types of rhythmic oscillations. Circadian rhythms such as our sleep/wake cycle follow an approximately 24 hour period. Ultradian rhythms follow a period shorter than 24 hours and include stress-induced pulses of cortisol.

Infradian rhythms follow a period longer than 24 hours and include the menstrual cycle. All of these rhythms are important to some degree for our physiology.

Circadian rhythms are particularly important because they regulate factors such as stem cell function, mitochondrial quality control, mood, and our immune response. These factors are essential in the maintenance of homeostasis, and thus, staying healthy.

We previously covered how essential circadian rhythms are to optimal health in a blog you can check out here.

Responses to stress

Stress is an unavoidable consequence of being alive. Many people take a myopic view of stress as something that is bad for us, but stress is essential to making us resilient. For example, the first time an athlete is exposed to competition or student to public speaking, they may not do so well.

The best way to become comfortable with either of the above scenarios is to expose yourself to them more frequently. In much the same way, our cells and organs become more resilient to stressors the more they experience them.

However, it’s important that the magnitude of each stressor as well as the cumulative effects are managed appropriately. It’s important that we can recover from a stressor, and that we allow ourselves sufficient time to do so.

We’ve covered the importance of building resilience at the organ level as well as total health in a blog you can check out here.

Homeostatic resilience

As previously mentioned, it’s important that we maintain homeostasis to maintain health. When we cannot maintain homeostasis within a system, there is a health cost associated with it. For example, chronic hyperglycemia causes damage to small blood vessels and nerves throughout the body.

Resilience builds in a reserve capacity such that when we slip out of homeostasis, we quickly return to it. For example, someone who exercises regularly may experience acute hyperglycemia if they eat a lot of cake. But they”ll eventually return to healthy blood glucose levels relatively quickly.

Those with Type 2 diabetes don’t have this homeostatic resilience, and therefore, they are unable to return to homeostatic blood glucose levels even over the long term.

Hormetic regulation

Hormesis is a process through which exposure to a small stressor, within the range that we can tlerate, helps build up tolerance to a larger stressor over time. For example, someone who has never run before likely wouldn’t be able to run 5 miles. Even if they could, it would hurt.

But if you start the same person with a 1 mile walk/jog and slowly build up their exposure to running, they may eventually tolerate 5 or even 10 miles. Exercise is a classic example of a hormetic stressor.

At the cellular level, exercise increases our need for energy, which puts hormetic stress on our mitochondria. If we keep doing this, and expose them to a level of stress they can overcome, our mitochondria become more efficient at generating energy.

In the same way, exposing our cells to small doses of free radicals builds up their antioxidant systems so that they can deal with higher levels of oxidative stress.

Repair and regeneration

A critical aspect of hormesis is that the level of stress we expose ourselves, our cells, and our organs to doesn’t exceed our ability to repair the damage. For example, exposing our skin to UV radiation causes our skin to become more resilient to UV damage.

If the UV exposure is within our limits to repair it, we get a tan which protects the DNA in our skin from further exposure to UV radiation. However, if we expose our skin to too much UV radiation we burn, increasing DNA damage and inflammation. Over time, repeated exposures can lead to skin cancer.

Conclusion

Staying healthy is a product of how well you compartmentalize infection and trauma, maintain homeostasis, and respond to stressors. Impairment in any of these factors increases the risk of infectious and chronic disease.

These factors should not be looked at in isolation, as deficiency in one capacity often comes with others. For example, people with Type 2 diabetes have deficiencies in many of these keys to health.

• Poor integrity of barriers–Hyperglycemia causes leaky gut and people with T2D have a leaky blood-brain barrier
• Poor containment of perturbations-via systemic inflammation
• An inability to maintain blood glucose homeostasis-due to beta cell apoptosis, poor integration of organ systems, and circadian disruption
• Low homeostatic resilience-Consumption of a carb load leads to hyperglycemia
• Poor repair/regeneration-Damage to blood vessels and nerves outpaces the capacity to repair/regenerate

Type 2 diabetes is also a perfect example of how both age and our lifestyle play an important role in staying healthy. Many of the age-related factors that alter the above abilities can be slowed by our behaviors.

Things like exercise, increasing physical activity, eating a balanced diet, getting better sleep, practicing good circadian behaviors, and managing stress.

Make it a priority to bolster these 8 key factors to staying healthy and you’ll be more likely to live a long, fruitful, happy life.