New research has systematically defined health at multiple levels, including whole tissues, organs, cells, subcells and molecules.
In a crude sense, health means "not being sick." But this simple definition does not really satisfy our understanding of health. A landmark review published in cell, a leading academic journal, details eight core markers of health, providing a systematic new definition of health at multiple levels, including the whole tissue, organ, cell, subcellular and molecular levels.
The authors are professor Carlos Lopez Otin of the University of Oviedo, Spain, whose research focuses on cancer, aging and genome function analysis. The other is Professor Guido Kroemer of the Gustave Roussy Institute in France, who has done much pioneering work in the fields of cell biology and cancer research.
Sign 1: Barrier intact
The skin, gut, and respiratory tract provide a barrier between us and our environment. In addition, there are barriers of different scales in our body, such as the blood-brain barrier, the cell membrane, and the membrane structure of mitochondria and nucleus. These barriers allow specific substances or molecules to enter specific areas, and their integrity is essential for maintaining health.
The blood-brain barrier, for example, acts as a brain filtration system. It is a tightly knit network of nerve and vascular cells that restricts circulating bacteria and inflammation-causing chemicals from entering brain tissue. "Leakage" of the blood-brain barrier has been linked to a variety of neurological diseases.
Sign 2: Contain local changes
Tiny local changes are constantly occurring in the human body, sometimes caused by external forces, sometimes pathogen invasion, but also may be the failure of DNA repair, protein accumulation caused by various "accidents" in the process of cell division. Failure to eliminate these "errors" or prevent the spread of errors can eventually lead to systemic disease.
The various local changes (red) have different health consequences when contained (purple) and overactivated (black)
Flag 3: Recycle and update
Proteins, lipids, nucleic acids and other molecules necessary for life processes will be modified by oxidation or spontaneously denaturated and degraded, resulting in cell damage; At the same time, external stress can also lead to accelerated injury. Therefore, most cell components and most cell types must be recycled constantly, which means that cells undergo active death, elimination, and replacement. The occurrence and development of many diseases associated with aging are closely related to the obstacles in the regeneration process.
Mechanisms of tissue and cell recycling and renewal
Autophagy may be considered the most important intracellular recovery mechanism, the authors note. In animal studies, genetic manipulation, caloric restriction, fasting, inhibition of insulin signaling, or some medications have contributed to a longer healthy life span, and the mechanism has been associated with autophagy. In addition to its anti-aging activity, drug-enhanced autophagy has been shown to have a broad impact on a wide range of important diseases, such as inherited mitochondrial diseases, metabolic syndrome, arteriosclerosis, hepatic steatosis, and a variety of neurodegenerative diseases.
Flag 4: Network "Integration"
Maintaining a healthy organism involves "integration" between different networks. From the structure of cells, to tissues and organs, to the human body and microbiome, different networks are intertwined, with many elements performing several roles simultaneously at different levels.
This means that the disease is not a "local" pathology. For example, there is growing evidence that common mental disorders, such as treatment-resistant depression, are associated with metabolic syndrome; Mental or metabolic disorders, as well as cancer, have been linked to changes in the gut flora.
Sign 5: Rhythm and cycle
Precise timing is crucial for living things. Heart rate, breathing, electrical brain activity, bowel movement, and many other key organs depend on certain rhythms for their function. The secretion of hormones and the activity of some cytokines also fluctuated in different cycles.
One type of circadian rhythm that has received the most attention is the roughly 24-hour circadian rhythm, also known as the body clock. Changes in circadian rhythms from a variety of causes, including shift work, irregular sleep patterns, poor sleep quality, frequent travel across time zones, and disrupted eating times, are known to be associated with an increased risk of a variety of diseases, including cancer, depression, diabetes, and disrupted gut flora.
Marker 6: Resilience of homeostasis
Body temperature, body weight, blood ph, blood sugar, blood pressure, blood oxygen concentration, hormone concentration and countless other biological parameters are usually maintained at nearly constant levels. Changing parameter Settings often leads to chronic disease. A typical example of the importance of homeostasis is the imbalance of too little or too much of a hormone.
This homeostasis resilience is linked to genetics, neurology, metabolism, immunity, and the human microbiome. In the case of gut microbiota, bacterial composition and activity for the same individual are usually established in childhood and show strong resilience thereafter, although there is considerable variation between individuals. This resilience protects against the pathologic effects associated with dysbiosis, such as inflammatory bowel disease, metabolic syndrome, cardiovascular dysfunction, asthma, colon cancer, and autism spectrum disorders.
The elastic mechanisms fail, eventually leading to aging and disease. Interventions aimed at increasing homeostasis resilience are expected to improve health.
Marker 7: regulation of the hormetic effect
Toxoexcitatory effect refers to the fact that exposure to a low dose of a toxin induces a protective response against damage from exposure to a higher dose of the same toxin. The term is also widely used to describe low-dose stressors (e.g., oxidative stress) that cause adaptive responses in cells and organisms, maintain homeostasis, and increase biological plasticity, the authors note.
Many studies are exploring how this biological process can be used in animal models to improve health, such as stabilizing the genome, scavenging free radicals and extending healthy life by means of low-dose radiation, low-concentration of certain chemicals and low-intensity dietary interventions.
Sign 8: Repair and regeneration
Repairs must be made for various injuries that threaten health. These damage and repair involve DNA and protein molecules, as well as organelles such as endoplasmic reticulum, mitochondria and lysosomes.
Where possible, damaged or lost functional components also need to be regenerated to achieve full recovery. Human stem and progenitor cells have the ability to repair damaged tissue and promote adaptive, compensatory responses. Even stem cells with the potential to repair have been found in the adult brain, an organ long thought unrepairable.
Stem cell-based regenerative medicine offers an alternative to cell and organ transplantation, promising to repair diseased or aging tissues and organs. The combination of induced pluripotent stem cells, CRISPR-Cas9 gene editing and other new technologies is bringing new treatments for congenital genetic defects, age-related diseases and helping reshape people's health.
The eight markers integrate multiple functions of each layer, coordinate complex interactions between different cells and subcells, and provide a multidimensional basis for health.
At the end of the review, the authors conclude that these biological markers of health include spatial separation, homeostasis over time, and a range of responses to stress. This new set of definitions provides an important reference for the measurement of physical function, mental health and the use of specific medical methods to examine the normal function of organs.
The article also emphasizes that these markers cannot be seen in isolation, but are interrelated, and problems in any one of them can become a risk factor, causing acute or sustained damage to the health of the whole body.
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