Microscopic health has eight dimensions! Cell article defines health

What is health?

A healthy person is considered to be in good physical, mental and social condition at a macro level. A recent article in Cell defines health from a micro and systemic perspective.

According to the authors, Carlos López Otín from the University of Oviedo and Guido Kroemer from the Gustave Roussy Institute in Spain, health is the maintenance of physiological tissue integrity and homeostasis.

The article explains the eight dimensions of health, covering the integrity of the body's barrier to the outside world, the suppression of local "turbulence" in the body, the maintenance of homeostasis over time, and appropriate response to stress.

The authors point out that disruption of any link in this interconnected chain can lead to the onset of disease, which in turn can cause acute or progressive derailment of the system, thus compromising health.

Figure 1 The eight dimensions of health

1. Barrier integrity: an important line of defense for maintaining health

In addition to the skin, intestines, and respiratory tract that isolate the body from the outside world, barriers also include the blood-brain barrier, cell membrane, and subcellular membrane structures. The integrity of these barriers only issues "passes" to specific substances or molecules, which is very important for maintaining health.

2. Inhibit local changes in the body: minimize damage

The body will constantly undergo small local changes, including external injuries, pathogen infection, inflammation caused by sterile damage, DNA repair failure, accumulation of erroneous proteins, etc. If these accidents cannot be contained and continue to go wrong or spread, they may lead to systemic diseases.

Figure 2. Impact of disruption of barrier integrity and local changes on health

3. Clear, recycle and renew: make the body healthier and younger

Proteins, lipids, nucleic acids, etc., if oxidatively modified or spontaneously denatured or degraded, will cause cell damage, and external stress will accelerate the damage. The body needs to remove and renew cells and cell components in a timely manner. The occurrence and development of many aging-related diseases are related to renewal disorders.

The turnover of the entire cell involves the coordination of regulated cell death, endocytosis, and replacement. Autophagy is the most important cytoplasmic recycling mechanism. In addition to being associated with anti-aging, promoting autophagy through drugs has also shown a wide range of effects on a variety of diseases, such as hereditary mitochondrial diseases, metabolic syndrome, atherosclerosis, fatty liver, and various neurodegenerative diseases.

Figure 3 Recycling and turnover mechanisms in tissues and cells

4. Network integration: looking at the disease as a whole

Disease is not a local change but should be viewed as a whole because different networks within the body, from intracellular structures, tissues and organs to the microbiome, are intertwined and influence each other.

For example, studies have shown that common mental illnesses are associated with metabolic syndrome, and mental illnesses, metabolic disorders, and cancer are related to changes in intestinal microorganisms.

5. Circadian rhythms and cycles: precise timing control is important

The human body is like a precision instrument, and precise timing control is essential to maintaining health. Heartbeat, breathing, brain electrical activity, intestinal peristalsis and other functions all have certain rhythms; hormone secretion and changes in the activity of some cytokines also have different periodic fluctuations.

The most well-known of these is the biological clock. Disorders of the biological clock caused by various reasons are associated with the risk of cancer, mental and psychological diseases, metabolic diseases, etc.

Figure 4 Precise timing control and the interweaving of networks at different levels, including molecules, subcellular, cells, tissues and organs, as well as the whole body, work together to maintain the health of the body.

6. Homeostatic elasticity: maintaining a stable internal environment

The body temperature, blood pH, blood sugar, blood pressure, blood oxygen concentration, hormone levels, etc. of a healthy human body must always be maintained within a certain range. The maintenance of this steady state is related to genetic factors, neurohumoral regulation, the immune system, and the microbiome. Interventions that promote the maintenance of steady state may help promote health.

Figure 5 Under different stress conditions, the body maintains homeostasis at different levels

7. Improving health through regulation of hormesis

The hormesis effect is a micro-disturbance of the body's homeostasis by low-dose poisons, which initiates a series of repair and maintenance mechanisms, such as increasing the expression of cell protection and repair proteins through the activation of transcription factors and kinases.

There are currently many animal experiments exploring the use of this effect to promote health, such as exposure to low-dose radiation, certain chemicals, etc. to achieve protective effects such as stabilizing the genome and removing free radicals, thereby prolonging life.

8. Repair and regeneration

For various injuries, the body's repair and regeneration functions are important. The body's stem cells and progenitor cells have the ability to repair damaged tissues and promote adaptive and compensatory responses. Currently, the combination of stem cell-based regenerative medicine, induced pluripotent stem cells, CRISPR-Cas9 gene editing and other new technologies is expected to bring new treatment methods in repairing injuries, aging and congenital genetic defects.

Source: López-Otín C, Kroemer G. Hallmarks of Health. Cell. 2020 Dec 15: S0092-8674(20)31606-8.

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