There are nine processes – the hallmarks of aging – that lead to decreased body functions and cause aging. Which aging hallmarks are there, and how can you stop them?
What drives the biological aging of our bodies? What are the underlying causes of decreased organism function and disease? Scientists found the answer – they defined nine different processes that lead to the decline and loss of body functions. These processes are called the hallmarks of aging. Read on and learn which hallmarks of aging there are and how you can reverse them.
What are the hallmarks of aging?
The hallmarks of aging, also known as the hallmarks of senescence, are the biological and chemical changes that occur to your body cells, tissues, and organs when you age. These changes negatively affect your body’s systems and lead to progressive loss of function (1). Moreover, this decline increases the risk that you will develop diabetes, cancer, heart diseases, or cognitive disorders.
The nine hallmarks of aging
In 2013,researchers defined nine hallmarks of aging (1):
- Genomic instability
- Telomere attrition
- Epigenetic alterations
- Loss of proteostasis
- Deregulated nutrient-sensing
- Mitochondrial dysfunction
- Cellular senescence
- Stem-cell exhaustion
- Altered intercellular communication
How can you stop them?
Is it even possible? Yes, in many cases, you can reverse the aging hallmarks, or at least slow them down. They are influenced by your diet, physical activity, supplements, and other factors. If you address them all together, you can promote your healthy longevity and extend the number of healthy years in your life.
Now, let’s have a look at the individual hallmarks of senescence and how you can reduce them.
1. Genomic instability
Various factors, both internal and external, cause damage to the DNA. Usually, the body has repair mechanisms to fix this damage – to put things into perspective, your DNA repair mechanisms fix about 20,000 damaging events per cell daily(2, 3). However, these mechanisms might fail.
When the repair mechanisms fail, DNA damage propagates (1). And since your DNA contains the "keys" used to produce proteins, enzymes, and other products that your body needs for functioning, its damage leads to the production of wrong or harmful substances (4, 5). As a result, your aging accelerates, and the risk of age-related diseases increases.
Diseases caused by genomic instability
What kind of diseases does genomic instability cause? Studies have shown that DNA damage could lead to:
- accelerated aging
- cancer
- degenerative diseases (4, 5, 6)
How to reduce genomic instability?
To fight the adverse effects of DNA damage, and to boost DNA repair mechanisms, try dietary restriction, such as intermittent fasting and caloric restriction (4, 7, 8). In addition, you can improve genomic stability by exercising and regular physical activity (9, 10).
How much and what exactly should you eat? What is the ideal amount of exercise? That’s different for every person. It’s ineffective, or even harmful, to follow universal, all-size-fits-all advice – every body is simply different. To learn what changes will be beneficial for you, you should test your biomarkers and create your plan based on the results. Book a free consultation to learn how we can help you with this.
2. Telomere attrition
Telomeres are protein structures that cap the ends of chromosomes, protecting the genome from degrading (1, 11, 12, 13). Every time a cell divides, telomeres shorten, until they reach the limit where they cannot shrink anymore. At this stage, which happens after around 50–60 division rounds, the cell cycle stops, and the cell starts to die (14, 15).
Telomere shortening is part of the natural process of the cell cycle. However, some factors accelerate the attrition rate – oxidative stress, inflammation, and chronic stress. They lead to a shorter cell cycle, and thus negatively affect your biological age and longevity (1).
Telomeres are maintained by an enzyme called telomerase, deficiency of which has been associated with the premature development of several diseases and the loss of tissue regenerative capacity.
Diseases caused by telomere shortening
Faster telomere shortening leads to accelerated aging (16). What kind of diseases does faster telomere attrition contribute to? It leads to autoimmune diseases, and increases the risk of cancer, heart conditions, infectious diseases, respiratory disorders, and psychological diseases.
How to slow down telomere shortening?
You can reduce this hallmark of aging by maintaining proper levels of vitamins C, E, and beta-carotene (17). Also, omega-3 fatty acids intake can slow down the rate of telomere attrition. For some people, it is beneficial to adapt a high-fiber, low-protein diet, increase the amount of physical activity, and reduce caloric income (17). Meditation and yoga can positively affect telomeres as well (18, 19).
But remember – every body is different, and only undergoing telomere testing can tell you what exactly will work for you. It provides a detailed analysis of your cellular health and serves as a foundation for continual improvement. Get your telomere length tested and find out what will help you improve it.
3. Epigenetic alterations
Epigenetic alterations are changes that lead to a change in the products your genes produce, without affecting the DNA sequence (1, 20). Epigenetic changes involve:
- DNA methylation
- post-translational modifications of histones
- chromatin remodeling
How does epigenetics work?
The alterations mentioned above are activated or deactivated by factors like enzymes, lifestyle, environment, and behavior (21). For example, when something activates DNA methylation, it adds a chemical group called methyl to a particular location on the DNA, turning it on. A similar rule applies to the other types of changes as well (22, 23).
Epigenetic dysregulation plays a crucial role in deteriorated cellular functions you can see in aging and age-related diseases (24). A higher burden of epigenetic changes could lead to cancer, diabetes, osteoporosis (a condition that makes bones fragile), neurological diseases, and increased inflammation levels (25).
How to fight epigenetic alterations?
Several interventions can attenuate the negative effects of epigenetic dysregulation. As the first step, you should get your epigenetics tested, to learn what exactly activates them in your body and which interventions will be beneficial for you. As a second step, you can implement these interventions. They are for example:
- caloric restriction
- probiotics, rapamycin, and spermidine supplementation
- Tai Chi
- optimizing sleep routine
- optimizing the levels of vitamins A, C, and D
- relaxation and breathing techniques
You physician should recommend you which of these are suitable for you, based on your epigenetics test results.
4. Loss of proteostasis
Proteostasis describes protein homeostasis, a process that ensures protein integrity (folding and recycling) within cells and organisms. There are many factors, both internal and external, that cause protein unfolding. So, when they fail to refold or degrade, they accumulate in the body and produce negative health effects (1). Proteostasis dysregulation is one of the nine hallmarks of aging.
How does it contribute to aging and disease development?
Young cells have mechanisms that help them regulate, degrade, and fold proteins. When these mechanisms become dysfunctional, proteins and their products accumulate (28). Such accumulation of abnormal or damaged protein due to loss of proteostasis can cause several diseases, like neurodegenerative diseases, heart disorders, and muscle-related conditions (29, 30).
How to improve protein functioning?
Various factors have negative effects on protein integrity and functioning – for example inflammation and stress. You can reduce these effects through several interventions, such as:
- specific diet changes (for example the Mediterranean diet)
- dietary supplements (like resveratrol, spermidine, berberine, curcumin, and quercetin)
- regular exercise (31, 32)
The interventions should always be based on the results of your diagnostics. Otherwise, they can be ineffective or even harmful. Book a free consultation with a longevity specialist to learn more.
5. Deregulated nutrient sensing
When nutrients are abundant, cells grow and develop. On the contrary, when nutrients are scarce, the cells direct their efforts to maintenance and repair. Nutrient sensing is the way in which cells respond to nutrients. When nutrient sensing deteriorates, it will affect and impair activities related to energy production, cell growth, and other vital functions (1). On the contrary, the regulation of nutrient sensing will promote longevity.
How does nutrient regulation work?
You can think of nutrient-sensing pathways as the link between aging and diet, activating and deactivating based on nutrient abundance or scarcity. Generally, nutrient-sensing pathways become deregulated with age, and gradually lose effectiveness and efficiency (33, 34).
Diseases caused by deregulated nutrient-sensing
Deregulated nutrient-sensing has been associated with several diseases, like heart conditions, metabolic disorders (for example type-2 diabetes), neurodegenerative conditions, sarcopenia (age-related loss in skeletal muscle strength and mass), and bone loss (35, 36, 37).
How to curb the effects of deregulated nutrient sensing?
Some interventions that modulate nutrient-sensing pathways are:
- caloric restriction
- intermittent fasting
- rapamycin and metformin supplementation (33, 37, 38).
Studies suggest that they work by mimicking the effects of nutrient scarcity, promoting maintenance and repair mechanisms. The outcome is promoted health and longevity.
- Do you know what are the levels of nutrients in your body? Visit our clinic and undergo a comprehensive analysis of your health.
6. Mitochondrial dysfunction
The mitochondrion is the location where most of the body's energy is produced. However, some factors can negatively affect its membrane integrity and make it dysfunctional. Mitochondrial dysfunction is one factor that accelerates aging in mammals, including humans (1, 39) – one of the nine hallmarks of aging.
The causes of mitochondrial dysfunction
One of the main drivers for mitochondrial dysfunction is the accumulation of reactive oxygen species – these are charged molecules that result from energy production activities. Another driver are enzyme deficiencies, such as DNA polymerase γ (an enzyme essential for mitochondrial DNA repair and replication).
Diseases caused by mitochondrial damage
Mitochondrial damage could predispose you to:
- neurodegenerative diseases
- cancers
- metabolic conditions
- muscle diseases
- heart-related problems (40, 41, 42)
How to fight mitochondrial dysfunction?
Just as there are factors that accelerate mitochondrial damage and fuel the aging process, there are others that could slow down, stop, or even reverse the adverse effects on the mitochondria.
Based on the evaluation of your mitochondrial health, medical professionals can recommend:
- vitamin D supplementation
- exercise and physical activity
- caloric restriction
- resveratrol and rapamycin supplementation (41, 43, 44)
7. Cellular senescence
Senescent cells are cells that don’t divide anymore. Accumulation of these cells, called cellular senescence, leads to negative consequences on the tissues. This cell type accumulates as we age and is triggered by internal and external factors, such as nutrition deprivation, tissue repair, mitochondrial dysfunction, radiation, or epigenetic modifications (1, 45).
Cellular senescence can both help and harm
Cellular senescence is not always bad. For example, in young cells, senescence prevents the growth of damaged cells and helps remove them, which ultimately stops cancerous cells from multiplying and increasing in numbers.
On the contrary, in old age, deficient clearance of senescent cells leads to their accumulation, causing harmful health effects (1, 45). This means that cellular senescence can be triggered by physiological or pathological factors, like DNA damage, telomere dysfunction, and other factors mentioned earlier (46).
Increased risk of disease
Cellular senescence, the seventh hallmark of aging, increases liability to diseases like neurodegenerative diseases, metabolic conditions, heart disorders, brain tumors, and frailty (46, 47, 48, 49). Fortunately, you can implement several interventions to remove accumulating senescent cells.
How to reduce cellular senescence?
One option to reduce cellular senescence is senolytics – molecules that selectively remove senescent cells. Examples include quercetin, fisetin, navitoclax, and others (46, 47). Another option is senomorphics – another class that modulates senescent cells but doesn’t remove them. Examples of such molecules include metformin, apigenin, rapamycin, and kaempferol (46, 47, 49).
Because cellular health is of uppermost importance, it is the main focus of one of our programs. The Cellular Regeneration program replaces non-functioning cells in the body with stronger and vital cells, which leads to the repair and regeneration of tissues and organs. We aim to provide a system reboot to make way for an improved qualify of life.
8. Stem cell exhaustion
Stem cells are young cells that can differentiate and become any cell (50, 51). They play a significant role in renewing, delaying, and preventing the aging of tissues and organs, and they hold substantial value in the fight to promote longevity. They decline with age and cause a deterioration in multiple systems, organs, and tissues (52).
With aging, stem cells become exhausted, and the regenerative capacity of many organs is compromised (1). For example, hematopoiesis (the formation of blood cellular components) is compromised with aging. That affects the body's capacity to produce immune cells, and increases the risk of infection. Rejuvenating stem cells could offer a solution to fight the aging process (1).
The risks of stem cell exhaustion
Stem cell exhaustion in adults could lead to cognitive decline, neurological degenerative diseases, delayed healing of tissues, reduced immune functionality, metabolic conditions, and heart-related diseases (53).
How can you improve stem cell health?
You can promote cell health by several diet-based interventions, like caloric restriction or fast-mimicking diet (54). Physicians might also recommend the supplementation of metformin, resveratrol, curcumin, and rapamycin. The interventions should always be based on your cell health diagnosis. You can learn more in a free consultation with a longevity specialist.
9. Altered intercellular communication
Cells communicate with each other via chemical and electrical means. This neurohormonal communication between cells is affected by age, inflammation, changes in the environment around the cell, and a decline in immune capacity (1).
The outcome is a change and decline in the mechanical and functional organ and tissue properties. In addition, it causes a phenomenon called inflammaging, which is the chronic inflammation in the elderly (34).
Conditions linked to intercellular communication
Intercellular communication is linked to conditions like cancer, frailty, dementia, and other diseases (1, 34).
How can you improve cellular communication?
Based on your specific biomarkers, physicians can recommend interventions like:
- exercising
- caloric restriction
- supplements, such as resveratrol, spermidine, and rapamycin (55, 56)
Are there more hallmarks of aging than nine?
The understanding of the nine hallmarks of aging is continuously updated, as scientists try to find new pathways that contribute to aging. As such, a group of researchers recently convened and updated the hallmarks of aging to include new ones:
- compromised autophagy
- microbiome disturbance
- altered mechanical properties
- splicing dysregulation
- inflammation (57)
Most of the newest hallmarks of aging were subcategories of the proposed hallmarks from 2013 (which are described in this article). However, further research and a better understanding of the hallmarks of aging in the period between 2013 and 2022 have led scientists to categorize them as standalone factors that drive the aging process.
Tying loose ends
We can divide the aging hallmarks in three categories:
- primary hallmarks of aging
- antagonistic hallmarks of aging
- integrative hallmarks of aging
The primary hallmarks of aging are considered the main drivers behind cellular damage and accelerated aging. They include genomic instability, telomere attrition, epigenetic changes, and loss of proteostasis (1).
The antagonistic hallmarks of aging represent the body’s response to damage, and at early stages, they produce beneficial effects. However, their chronic or exacerbated activation produces adverse health effects and accelerates aging. The antagonistic hallmarks are deregulated nutrient-sensing, mitochondrial dysfunction, and cellular senescence.
The integrative hallmarks of aging represent the primary reasons for functional decline observed with aging (1). These are stem cell exhaustion and altered cellular communication.
With personalized approach, you can reduce the hallmarks of aging
Studies confirm that you can attenuate, modulate, and even reverse the majority of the aging hallmarks with proper interventions. Generally, some of the widely recommended approaches are physical activity, a healthy diet, and adequate intake of micro- and macronutrients. In addition, supplements with certain properties can help reduce some of the negative effects of the hallmarks of senescence.
Under all circumstances, it is best to consult with certified healthcare professionals before adopting or initiating any interventions. They should always be based on your individual biomarkers and longevity diagnostics.
Personalized diagnostics and health plan to reduce the hallmarks of aging
At Healthy Longevity Clinic, you can undergo diagnostics which will reveal the impact of the aging hallmarks on your health, biological age, and longevity. You can measure your telomere length, cellular health, mitochondrial function, and much more. Based on your results, experts from our clinic, extensively trained in longevity, will design a personalized health plan – Longevity Roadmap – for you and give you specific recommendations to improve your health, reverse the hallmarks of aging, and achieve optimal longevity. Book a free consultation.
What drives the biological aging of our bodies? What are the underlying causes of decreased organism function and disease? Scientists found the answer – they defined nine different processes that lead to the decline and loss of body functions. These processes are called the hallmarks of aging. Read on and learn which hallmarks of aging there are and how you can reverse them.
What are the hallmarks of aging?
The hallmarks of aging, also known as the hallmarks of senescence, are the biological and chemical changes that occur to your body cells, tissues, and organs when you age. These changes negatively affect your body’s systems and lead to progressive loss of function (1). Moreover, this decline increases the risk that you will develop diabetes, cancer, heart diseases, or cognitive disorders.
The nine hallmarks of aging
In 2013,researchers defined nine hallmarks of aging (1):
- Genomic instability
- Telomere attrition
- Epigenetic alterations
- Loss of proteostasis
- Deregulated nutrient-sensing
- Mitochondrial dysfunction
- Cellular senescence
- Stem-cell exhaustion
- Altered intercellular communication
How can you stop them?
Is it even possible? Yes, in many cases, you can reverse the aging hallmarks, or at least slow them down. They are influenced by your diet, physical activity, supplements, and other factors. If you address them all together, you can promote your healthy longevity and extend the number of healthy years in your life.
Now, let’s have a look at the individual hallmarks of senescence and how you can reduce them.
1. Genomic instability
Various factors, both internal and external, cause damage to the DNA. Usually, the body has repair mechanisms to fix this damage – to put things into perspective, your DNA repair mechanisms fix about 20,000 damaging events per cell daily(2, 3). However, these mechanisms might fail.
When the repair mechanisms fail, DNA damage propagates (1). And since your DNA contains the "keys" used to produce proteins, enzymes, and other products that your body needs for functioning, its damage leads to the production of wrong or harmful substances (4, 5). As a result, your aging accelerates, and the risk of age-related diseases increases.
Diseases caused by genomic instability
What kind of diseases does genomic instability cause? Studies have shown that DNA damage could lead to:
- accelerated aging
- cancer
- degenerative diseases (4, 5, 6)
How to reduce genomic instability?
To fight the adverse effects of DNA damage, and to boost DNA repair mechanisms, try dietary restriction, such as intermittent fasting and caloric restriction (4, 7, 8). In addition, you can improve genomic stability by exercising and regular physical activity (9, 10).
How much and what exactly should you eat? What is the ideal amount of exercise? That’s different for every person. It’s ineffective, or even harmful, to follow universal, all-size-fits-all advice – every body is simply different. To learn what changes will be beneficial for you, you should test your biomarkers and create your plan based on the results. Book a free consultation to learn how we can help you with this.
2. Telomere attrition
Telomeres are protein structures that cap the ends of chromosomes, protecting the genome from degrading (1, 11, 12, 13). Every time a cell divides, telomeres shorten, until they reach the limit where they cannot shrink anymore. At this stage, which happens after around 50–60 division rounds, the cell cycle stops, and the cell starts to die (14, 15).
Telomere shortening is part of the natural process of the cell cycle. However, some factors accelerate the attrition rate – oxidative stress, inflammation, and chronic stress. They lead to a shorter cell cycle, and thus negatively affect your biological age and longevity (1).
Telomeres are maintained by an enzyme called telomerase, deficiency of which has been associated with the premature development of several diseases and the loss of tissue regenerative capacity.
Diseases caused by telomere shortening
Faster telomere shortening leads to accelerated aging (16). What kind of diseases does faster telomere attrition contribute to? It leads to autoimmune diseases, and increases the risk of cancer, heart conditions, infectious diseases, respiratory disorders, and psychological diseases.
How to slow down telomere shortening?
You can reduce this hallmark of aging by maintaining proper levels of vitamins C, E, and beta-carotene (17). Also, omega-3 fatty acids intake can slow down the rate of telomere attrition. For some people, it is beneficial to adapt a high-fiber, low-protein diet, increase the amount of physical activity, and reduce caloric income (17). Meditation and yoga can positively affect telomeres as well (18, 19).
But remember – every body is different, and only undergoing telomere testing can tell you what exactly will work for you. It provides a detailed analysis of your cellular health and serves as a foundation for continual improvement. Get your telomere length tested and find out what will help you improve it.
3. Epigenetic alterations
Epigenetic alterations are changes that lead to a change in the products your genes produce, without affecting the DNA sequence (1, 20). Epigenetic changes involve:
- DNA methylation
- post-translational modifications of histones
- chromatin remodeling
How does epigenetics work?
The alterations mentioned above are activated or deactivated by factors like enzymes, lifestyle, environment, and behavior (21). For example, when something activates DNA methylation, it adds a chemical group called methyl to a particular location on the DNA, turning it on. A similar rule applies to the other types of changes as well (22, 23).
Epigenetic dysregulation plays a crucial role in deteriorated cellular functions you can see in aging and age-related diseases (24). A higher burden of epigenetic changes could lead to cancer, diabetes, osteoporosis (a condition that makes bones fragile), neurological diseases, and increased inflammation levels (25).
How to fight epigenetic alterations?
Several interventions can attenuate the negative effects of epigenetic dysregulation. As the first step, you should get your epigenetics tested, to learn what exactly activates them in your body and which interventions will be beneficial for you. As a second step, you can implement these interventions. They are for example:
- caloric restriction
- probiotics, rapamycin, and spermidine supplementation
- Tai Chi
- optimizing sleep routine
- optimizing the levels of vitamins A, C, and D
- relaxation and breathing techniques
You physician should recommend you which of these are suitable for you, based on your epigenetics test results.
4. Loss of proteostasis
Proteostasis describes protein homeostasis, a process that ensures protein integrity (folding and recycling) within cells and organisms. There are many factors, both internal and external, that cause protein unfolding. So, when they fail to refold or degrade, they accumulate in the body and produce negative health effects (1). Proteostasis dysregulation is one of the nine hallmarks of aging.
How does it contribute to aging and disease development?
Young cells have mechanisms that help them regulate, degrade, and fold proteins. When these mechanisms become dysfunctional, proteins and their products accumulate (28). Such accumulation of abnormal or damaged protein due to loss of proteostasis can cause several diseases, like neurodegenerative diseases, heart disorders, and muscle-related conditions (29, 30).
How to improve protein functioning?
Various factors have negative effects on protein integrity and functioning – for example inflammation and stress. You can reduce these effects through several interventions, such as:
- specific diet changes (for example the Mediterranean diet)
- dietary supplements (like resveratrol, spermidine, berberine, curcumin, and quercetin)
- regular exercise (31, 32)
The interventions should always be based on the results of your diagnostics. Otherwise, they can be ineffective or even harmful. Book a free consultation with a longevity specialist to learn more.
5. Deregulated nutrient sensing
When nutrients are abundant, cells grow and develop. On the contrary, when nutrients are scarce, the cells direct their efforts to maintenance and repair. Nutrient sensing is the way in which cells respond to nutrients. When nutrient sensing deteriorates, it will affect and impair activities related to energy production, cell growth, and other vital functions (1). On the contrary, the regulation of nutrient sensing will promote longevity.
How does nutrient regulation work?
You can think of nutrient-sensing pathways as the link between aging and diet, activating and deactivating based on nutrient abundance or scarcity. Generally, nutrient-sensing pathways become deregulated with age, and gradually lose effectiveness and efficiency (33, 34).
Diseases caused by deregulated nutrient-sensing
Deregulated nutrient-sensing has been associated with several diseases, like heart conditions, metabolic disorders (for example type-2 diabetes), neurodegenerative conditions, sarcopenia (age-related loss in skeletal muscle strength and mass), and bone loss (35, 36, 37).
How to curb the effects of deregulated nutrient sensing?
Some interventions that modulate nutrient-sensing pathways are:
- caloric restriction
- intermittent fasting
- rapamycin and metformin supplementation (33, 37, 38).
Studies suggest that they work by mimicking the effects of nutrient scarcity, promoting maintenance and repair mechanisms. The outcome is promoted health and longevity.
- Do you know what are the levels of nutrients in your body? Visit our clinic and undergo a comprehensive analysis of your health.
6. Mitochondrial dysfunction
The mitochondrion is the location where most of the body's energy is produced. However, some factors can negatively affect its membrane integrity and make it dysfunctional. Mitochondrial dysfunction is one factor that accelerates aging in mammals, including humans (1, 39) – one of the nine hallmarks of aging.
The causes of mitochondrial dysfunction
One of the main drivers for mitochondrial dysfunction is the accumulation of reactive oxygen species – these are charged molecules that result from energy production activities. Another driver are enzyme deficiencies, such as DNA polymerase γ (an enzyme essential for mitochondrial DNA repair and replication).
Diseases caused by mitochondrial damage
Mitochondrial damage could predispose you to:
- neurodegenerative diseases
- cancers
- metabolic conditions
- muscle diseases
- heart-related problems (40, 41, 42)
How to fight mitochondrial dysfunction?
Just as there are factors that accelerate mitochondrial damage and fuel the aging process, there are others that could slow down, stop, or even reverse the adverse effects on the mitochondria.
Based on the evaluation of your mitochondrial health, medical professionals can recommend:
- vitamin D supplementation
- exercise and physical activity
- caloric restriction
- resveratrol and rapamycin supplementation (41, 43, 44)
7. Cellular senescence
Senescent cells are cells that don’t divide anymore. Accumulation of these cells, called cellular senescence, leads to negative consequences on the tissues. This cell type accumulates as we age and is triggered by internal and external factors, such as nutrition deprivation, tissue repair, mitochondrial dysfunction, radiation, or epigenetic modifications (1, 45).
Cellular senescence can both help and harm
Cellular senescence is not always bad. For example, in young cells, senescence prevents the growth of damaged cells and helps remove them, which ultimately stops cancerous cells from multiplying and increasing in numbers.
On the contrary, in old age, deficient clearance of senescent cells leads to their accumulation, causing harmful health effects (1, 45). This means that cellular senescence can be triggered by physiological or pathological factors, like DNA damage, telomere dysfunction, and other factors mentioned earlier (46).
Increased risk of disease
Cellular senescence, the seventh hallmark of aging, increases liability to diseases like neurodegenerative diseases, metabolic conditions, heart disorders, brain tumors, and frailty (46, 47, 48, 49). Fortunately, you can implement several interventions to remove accumulating senescent cells.
How to reduce cellular senescence?
One option to reduce cellular senescence is senolytics – molecules that selectively remove senescent cells. Examples include quercetin, fisetin, navitoclax, and others (46, 47). Another option is senomorphics – another class that modulates senescent cells but doesn’t remove them. Examples of such molecules include metformin, apigenin, rapamycin, and kaempferol (46, 47, 49).
Because cellular health is of uppermost importance, it is the main focus of one of our programs. The Cellular Regeneration program replaces non-functioning cells in the body with stronger and vital cells, which leads to the repair and regeneration of tissues and organs. We aim to provide a system reboot to make way for an improved qualify of life.
8. Stem cell exhaustion
Stem cells are young cells that can differentiate and become any cell (50, 51). They play a significant role in renewing, delaying, and preventing the aging of tissues and organs, and they hold substantial value in the fight to promote longevity. They decline with age and cause a deterioration in multiple systems, organs, and tissues (52).
With aging, stem cells become exhausted, and the regenerative capacity of many organs is compromised (1). For example, hematopoiesis (the formation of blood cellular components) is compromised with aging. That affects the body's capacity to produce immune cells, and increases the risk of infection. Rejuvenating stem cells could offer a solution to fight the aging process (1).
The risks of stem cell exhaustion
Stem cell exhaustion in adults could lead to cognitive decline, neurological degenerative diseases, delayed healing of tissues, reduced immune functionality, metabolic conditions, and heart-related diseases (53).
How can you improve stem cell health?
You can promote cell health by several diet-based interventions, like caloric restriction or fast-mimicking diet (54). Physicians might also recommend the supplementation of metformin, resveratrol, curcumin, and rapamycin. The interventions should always be based on your cell health diagnosis. You can learn more in a free consultation with a longevity specialist.
9. Altered intercellular communication
Cells communicate with each other via chemical and electrical means. This neurohormonal communication between cells is affected by age, inflammation, changes in the environment around the cell, and a decline in immune capacity (1).
The outcome is a change and decline in the mechanical and functional organ and tissue properties. In addition, it causes a phenomenon called inflammaging, which is the chronic inflammation in the elderly (34).
Conditions linked to intercellular communication
Intercellular communication is linked to conditions like cancer, frailty, dementia, and other diseases (1, 34).
How can you improve cellular communication?
Based on your specific biomarkers, physicians can recommend interventions like:
- exercising
- caloric restriction
- supplements, such as resveratrol, spermidine, and rapamycin (55, 56)
Are there more hallmarks of aging than nine?
The understanding of the nine hallmarks of aging is continuously updated, as scientists try to find new pathways that contribute to aging. As such, a group of researchers recently convened and updated the hallmarks of aging to include new ones:
- compromised autophagy
- microbiome disturbance
- altered mechanical properties
- splicing dysregulation
- inflammation (57)
Most of the newest hallmarks of aging were subcategories of the proposed hallmarks from 2013 (which are described in this article). However, further research and a better understanding of the hallmarks of aging in the period between 2013 and 2022 have led scientists to categorize them as standalone factors that drive the aging process.
Tying loose ends
We can divide the aging hallmarks in three categories:
- primary hallmarks of aging
- antagonistic hallmarks of aging
- integrative hallmarks of aging
The primary hallmarks of aging are considered the main drivers behind cellular damage and accelerated aging. They include genomic instability, telomere attrition, epigenetic changes, and loss of proteostasis (1).
The antagonistic hallmarks of aging represent the body’s response to damage, and at early stages, they produce beneficial effects. However, their chronic or exacerbated activation produces adverse health effects and accelerates aging. The antagonistic hallmarks are deregulated nutrient-sensing, mitochondrial dysfunction, and cellular senescence.
The integrative hallmarks of aging represent the primary reasons for functional decline observed with aging (1). These are stem cell exhaustion and altered cellular communication.
With personalized approach, you can reduce the hallmarks of aging
Studies confirm that you can attenuate, modulate, and even reverse the majority of the aging hallmarks with proper interventions. Generally, some of the widely recommended approaches are physical activity, a healthy diet, and adequate intake of micro- and macronutrients. In addition, supplements with certain properties can help reduce some of the negative effects of the hallmarks of senescence.
Under all circumstances, it is best to consult with certified healthcare professionals before adopting or initiating any interventions. They should always be based on your individual biomarkers and longevity diagnostics.
Personalized diagnostics and health plan to reduce the hallmarks of aging
At Healthy Longevity Clinic, you can undergo diagnostics which will reveal the impact of the aging hallmarks on your health, biological age, and longevity. You can measure your telomere length, cellular health, mitochondrial function, and much more. Based on your results, experts from our clinic, extensively trained in longevity, will design a personalized health plan – Longevity Roadmap – for you and give you specific recommendations to improve your health, reverse the hallmarks of aging, and achieve optimal longevity. Book a free consultation.
- López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-217.
- Brown TA. The human genome. Genomes 2nd edition: Wiley-Liss; 2002.
- Loeb LA. Human cancers express mutator phenotypes: origin, consequences and targeting. Nature Reviews Cancer. 2011;11(6):450-7.
- Vijg J, Montagna C. Genome instability and aging: Cause or effect? Translational Medicine of Aging. 2017;1:5-11.
- Niedernhofer LJ, Gurkar AU, Wang Y, Vijg J, Hoeijmakers JHJ, Robbins PD. Nuclear genomic instability and aging. Annual review of biochemistry. 2018;87:295-322.
- Vijg J, Suh Y. Genome instability and aging. Annu Rev Physiol. 2013;75:645-68.
- Mindikoglu AL, Abdulsada MM, Jain A, Choi JM, Jalal PK, Devaraj S, et al. Intermittent fasting from dawn to sunset for 30 consecutive days is associated with anticancer proteomic signature and upregulates key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system and cognitive function in healthy subjects. Journal of proteomics. 2020;217:103645.
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