Health is often defined simply as the absence of disease. However, in this article, we will delve into a more nuanced understanding of health. Here, health is not merely the lack of something negative, but rather, it is characterized by a series of dynamic features that actively maintain a state of well-being and stave off disease.
These features are known as the ‘Hallmarks of Health.’ This concept was proposed by the same pioneering researchers who introduced the ‘Hallmarks of Aging’ in 2013. The hallmarks of health provide a comprehensive framework that could potentially revolutionize our approach to medicine. Instead of focusing primarily on treating diseases after they occur, this ‘medicine of health’ would emphasize the importance of maintaining these hallmarks to prevent disease states from arising in the first place.
In the following sections, we will explore each of these hallmarks in detail, discussing their role in maintaining health and how they could be harnessed to prevent disease and promote overall well-being.
The 8 Hallmarks of Health
Just as with the hallmarks of aging, the authors established three criteria that must be met for a feature to qualify as a hallmark of health:
- It should be associated with a healthy state.
- Its experimental or real-life perturbation should lead to significant pathogenic effects.
- Its experimental or medical maintenance or restoration should demonstrate broad pro-health activity.
Interestingly, not all the hallmarks of health fully meet these criteria, particularly the third one as it was the case for the hallmarks of aging. This is largely due to the current lack of therapies and the need for further advancements in research.
The eight hallmarks are divided into three main categories:
- Spatial Compartmentalization
- Integrity of Barriers
- Containment of Perturbations
- Maintenance of Homeostasis Over Time
- Recycling and Turnover
- Integration of Circuitries
- Rhythmic Oscillations
- Adequate Responses to Stress
- Homeostatic Resilience
- Hormetic Regulation
- Repair and Regeneration
It’s important to understand that, although these hallmarks are categorized separately, they are highly interconnected. Changes in one hallmark are likely to be reflected in others, underscoring the complex and interdependent nature of our health.
In the following paragraphs, I will explore and give a brief overview of the proposed hallmarks of health and their significance in the context of longevity medicine.
Integrity of Barriers
The “Integrity of Barriers” emphasizes the importance of maintaining the physical barriers in our body that separate different compartments and protect us from external threats. These barriers include the skin, the lining of the gut, the blood-brain barrier, and the endothelial lining of our blood vessels. They serve as our first line of defense against pathogens and toxins, and also play a crucial role in preventing the leakage of substances between different compartments of the body. When these barriers are compromised, it can lead to a variety of health issues, including inflammation, infection, and autoimmune disorders. Therefore, maintaining the integrity of these barriers is essential for overall health.
Containment of Perturbations
Containment of Perturbations refers to the body’s ability to limit the spread and impact of disturbances or changes that could potentially harm it. These perturbations can be internal, like a senescent cell, or external, like exposure to a pathogen. The body has various mechanisms to contain these perturbations, including immune responses, feedback loops in metabolic processes, and cellular repair systems. For example, if a pathogen invades, the immune system works to contain the spread. If a metabolic imbalance occurs, feedback mechanisms work to restore balance. The ability to effectively contain perturbations is crucial for maintaining health and preventing disease. When this capacity is compromised, it can lead to a cascade of issues that may ultimately result in disease.
Recycling and Turnover
Recycling and Turnover refers to the body’s ability to continuously renew and recycle its components. This process is vital for maintaining the functionality and health of cells and tissues. For instance, autophagy, a cellular process where damaged components are broken down and recycled, is a key aspect of this hallmark. Similarly, the turnover of cells, where old or damaged cells are replaced with new ones, is crucial for maintaining tissue health. This includes processes like the constant renewal of skin cells, red blood cells, and the lining of the gut. When these recycling and turnover processes are functioning optimally, they contribute to the maintenance of health. However, if they become impaired, it can lead to the accumulation of damaged cells and components, potentially leading to various health issues and diseases.
Integration of Circuitries
Integration of Circuitries refers to the complex network of communication and coordination among various systems within the body. This includes the integration of metabolic, hormonal, and neuronal circuits, which work together to maintain homeostasis and respond to changes in the internal and external environment. For instance, the integration of the nervous and endocrine systems allows the body to respond appropriately to stress, while the coordination between the digestive system and the brain helps regulate appetite and energy balance. When these integrated circuitries function properly, they contribute to overall health by ensuring that all parts of the body work in harmony. However, disruptions in these integrated networks can lead to imbalances and potentially contribute to the development of various health conditions.
Rhythmic Oscillations is a hallmark of health that refers to the various biological rhythms that govern our bodies. These include circadian rhythms, which follow a roughly 24-hour cycle and regulate many physiological processes such as sleep-wake cycles, feeding, and hormone production. Other rhythms include the cardiac cycle, respiratory rhythms, and even cellular cycles like the cell division cycle. These rhythms are crucial for synchronizing our biological functions with environmental cues (like light and dark) and for coordinating various internal processes. When these rhythms are in sync, they contribute to overall health and well-being. However, disruptions in these rhythms, such as those caused by shift work, jet lag, or various health conditions, can have adverse effects on health, affecting everything from sleep quality to metabolic processes and leading to the development of chronic disease.
Homeostatic Resilience refers to the body’s ability to maintain or return to a state of balance or equilibrium in response to stressors or changes in the environment. Several biological parameters like blood pH, blood pressure, glycemia, and body temperature are maintained at a constant level by homeostatic processes. These parameters may also change temporarily in response to a stressor or stimuli before returning to their steady state. Homeostatic resilience involves a variety of physiological processes and systems, including the immune system, the endocrine system, and the nervous system, among others. For instance, when faced with an infection, the immune system responds to eliminate the pathogen and then returns to its baseline state. Similarly, after physical exertion, the body works to restore energy balance and repair any tissue damage. This resilience is crucial for maintaining health and preventing disease. When homeostatic resilience is compromised, it can lead to chronic inflammation, metabolic disorders, and other health issues. Therefore, maintaining homeostatic resilience is a key aspect of health.
Hormetic Regulation refers to the body’s ability to respond positively to mild stressors, a phenomenon known as hormesis. Hormesis is a biological response where a beneficial effect (improved health, stress tolerance, growth, or longevity) results from exposure to low doses of an agent or activity that is otherwise toxic or lethal when given at higher doses. Examples of hormetic stressors include moderate exercise, intermittent fasting, or exposure to heat or cold. These stressors activate adaptive response pathways in the body that can lead to enhanced repair, maintenance, and functionality. Essentially, what doesn’t kill us (in small doses) can make us stronger. However, the key to hormetic regulation is balance, as too much stress can be harmful. Understanding and harnessing hormetic regulation can be a powerful strategy for promoting health and longevity.
Repair and Regeneration
Repair and Regeneration refers to the body’s ability to repair damage and regenerate tissues. This process is crucial for maintaining the health and functionality of our bodies. For instance, when a wound occurs, a complex cascade of events is triggered to repair the damage, involving inflammation, new tissue formation, and tissue remodeling. Similarly, certain tissues in our bodies, such as the liver and skin, have a remarkable capacity to regenerate after injury. On a cellular level, mechanisms like DNA repair help maintain the integrity of our genetic material. When these repair and regeneration processes are functioning optimally, they contribute to health and longevity. However, if they become impaired, it can lead to the accumulation of damage and potentially contribute to aging and various diseases. Therefore, maintaining the capacity for repair and regeneration is a key aspect of health.
The difference between this hallmark and the third one, recycling and turnover, which may seem similar is that the former is triggered by specific cell signaling and stimuli that depend on specific types of damage and which will trigger specific well-defined responses, while the latter happens without specific stimulation.
- Hallmarks of Health
C Lopez-Otin – Cell, Dec 2020