April 12

_LEARN

/

REFERENCE LAB

How chronic stress makes you age faster

From work pressures to unexpected visits from the in-laws, daily stress is a reality of life. With a healthy lifestyle, most of us bounce back from intermittent stress and return to a balanced state. But for some of us, relief never comes. Chronic stress, defined as a persistent sense of feeling pressured and overwhelmed over a long period of time, takes an incredible toll on our bodies.¹ In fact, studies have shown that chronic stress increases multiple hallmarks of aging, speeds the rate at which we age, and increases our risk for numerous age-related diseases. Join us as we dig into the science and explore the compelling reasons why managing stress might be one of the most important things you can do for your longevity.







_LEARN

/

REFERENCE LAB

April 12

How chronic stress makes you age faster

From work pressures to unexpected visits from the in-laws, daily stress is a reality of life. With a healthy lifestyle, most of us bounce back from intermittent stress and return to a balanced state. But for some of us, relief never comes. Chronic stress, defined as a persistent sense of feeling pressured and overwhelmed over a long period of time, takes an incredible toll on our bodies.¹ In fact, studies have shown that chronic stress increases multiple hallmarks of aging, speeds the rate at which we age, and increases our risk for numerous age-related diseases. Join us as we dig into the science and explore the compelling reasons why managing stress might be one of the most important things you can do for your longevity.







01 Chronic stress induces cellular senescence

A chronic state of mental stress is a risk factor for numerous diseases. To understand why, scientists have examined the underlying similarities between these diseases. The common feature seems to be cellular senescence, the accumulation of dead “zombie” cells that secrete harmful biochemical signals–inducing chronic inflammation, suppressing the immune system, and accelerating aging in neighboring cells.²

With cellular senescence as a common link between stress-related diseases, scientists took a closer look to determine whether chronic stress itself functionally increases rates of cellular senescence. In a study, researchers asked 73 adults to self-report their stress levels. Each participant also donated a blood sample that scientists used to measure P16ᴵᴺᴷ⁴ᵃ, a key marker of cellular senescence. Individuals with greater chronic stress exposure showed higher levels of P16ᴵᴺᴷ⁴ᵃ, indicating higher overall levels of cellular senescence.³

Cellular senescence is associated with cancer, cardiovascular, neurodegenerative and autoimmune disorders. While many of these diseases are age-related, there is some evidence showing that persistent, severe stress can trigger them earlier in a person’s life. This may be due in part to a phenomenon called immunosenescence, senescence in immune cells. When increasing numbers of immune cells become senescent, the body experiences a deterioration in immune response not normally seen in younger people. This can lead to the development and acceleration of two additional aging hallmarks: telomere attrition and chronic inflammation.²

02 Chronic stress increases inflammaging

Like stress, inflammation is a normal part of the human experience. It’s the body’s main way of identifying harm–whether from pathogens or injury–and initiating the healing process. Acute, or short-term inflammation, is essential to our health. But when that same inflammation becomes constant, it can actually do more harm than good.⁴

Chronic inflammation, also known as inflammaging, is age-associated inflammation caused by alterations in the body’s immune response. It’s now understood that these alterations occur when the body’s immune response is disrupted due to immunosenescence. This continuous, systemic inflammation can contribute to the development of several diseases including atherosclerosis, diabetes, and hypertension.

In addition to its link with stress-induced cellular senescence, inflammaging is also believed to be directly tied to chronic psychological stress by altering levels of cytokines, small proteins that are important in cellular signaling. During the aging process, the body experiences a decrease in anti-inflammatory cytokines, and a simultaneous increase in pro-inflammatory cytokines, leading to overall higher levels of inflammation. Scientists now believe that chronic psychological stress further stimulates pro-inflammatory cytokines. In fact, some studies have shown that antidepressants, which are used to reduce psychological stress, actually reduce enhanced levels of these pro-inflammatory cytokines.²

This data indicates that living in a constant state of psychological stress can actually accelerate the inflammaging that you might normally experience as a result of the aging process–hastening the cellular damage caused by inflammation so that you actually age more quickly.

03 Chronic stress induces telomere attrition

In addition to its effects on cellular senescence and inflammation, research shows that chronic stress can have a structural impact on our chromosomes, tightly packed molecules that house our DNA.

Telomeres are protective casings located at the end of each chromosome that shield our chromosomes from becoming frayed or tangled. Because our telomeres shorten every time a cell divides, our telomere length naturally shortens with age. Once telomeres become too short, cells experience senescence, cell death, or oncogenic transformations where they can become cancerous. Shorter telomeres have been associated with increased risk for diseases and overall shorter lifespan.⁶

When we’re young and healthy, telomere attrition is kept at bay with telomerase, an enzyme that replenishes telomere length even as our cells continue to divide. However, chronic stress–and constantly high levels of the stress hormone cortisol–decreases the body’s natural supply of telomerase. This means that chronic stress can actually speed the rate at which we experience telomere attrition, accelerating its systemic aging effects. ⁷

04 Chronic stress increases oxidative stress

You know you should be eating a lot of antioxidant-rich fruits and veggies, but do you know why? It’s because antioxidants naturally combat reactive oxygen species (ROS), unstable molecules also known as free radicals that can damage our cells, alter cellular metabolism, and increase inflammation.

From the time we are born, our cells are constantly managing ROS. But our ability to neutralize ROS can wane as we age, leading to oxidative stress–a phenomenon associated with physical signs of aging. Interestingly, within the body, the main source of ROS is actually our own mitochondria, which become dysfunctional as a result of inflammaging.²

Our ability to fend off oxidative stress becomes further impaired when we experience a constant state of psychological stress. In a study, scientists compared patients with PTSD to control individuals and discovered that people with PTSD show signs of reduced ROS metabolism. This means that they experience higher rates of oxidative stress. Because oxidative stress itself seems to trigger crosstalk between the immune and central neural systems, scientists believe that stress-induced oxidative stress may actually create a pernicious cycle that further degrades emotional wellbeing, leading to more psychological stress.²

05 Putting it all together

Once you dig into the science, it’s easy to see that everything is connected. Increased cellular senescence, inflammaging, telomere attrition, and oxidative stress are all magnified by one another. In short, chronic stress kicks off a cascade of accelerated aging factors that amplify one another, creating system-wide impacts. This underlines the incredibly damaging potential of living a life with unregulated stress levels.

So how can you help manage chronic stress? In addition to seeking out mental health help from a therapist, experts recommend getting regular exercise, prioritizing sleep, making time for leisure activities and practicing mindfulness. While these tactics may seem mundane in the face of major psychological stress, small daily lifestyle shifts can help the body recover both mentally and physically from a state of chronic stress.¹

06Key Takeaways

  • Studies have shown that chronic stress speeds the rate at which we age, and increases our risk for numerous age-related diseases.
  • Individuals with chronic stress show higher markers of cellular senescence, a central hallmark of aging tied to cancer, cardiovascular, neurodegenerative and autoimmune disorders.
  • Chronic psychological stress also stimulates pro-inflammatory cytokines and systemic inflammation, a factor linked to several diseases including atherosclerosis, diabetes, and hypertension.
  • Constant exposure to the stress hormone, cortisol, decreases the body’s natural supply of telomerase, an enzyme that prevents telomere attrition, a hallmark of aging linked to diminished lifespan.
  • Higher rates of psychological stress are linked to increased oxidative stress, the overproduction of free radicals that damage our cells and induce inflammation.
  • Regular exercise, prioritizing sleep, making time for leisure activities and practicing mindfulness can help mitigate the psychological and physical impacts of chronic stress.
References
[1] https://www.yalemedicine.org/conditions/stress-disorder
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400286/
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420375
[4] https://www.ncbi.nlm.nih.gov/books/NBK493173/
[5] https://www.genome.gov/genetics-glossary/Telomere
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370421/
[7] https://www.apa.org/monitor/2014/10/

    01 Chronic stress induces cellular senescence

    A chronic state of mental stress is a risk factor for numerous diseases. To understand why, scientists have examined the underlying similarities between these diseases. The common feature seems to be cellular senescence, the accumulation of dead “zombie” cells that secrete harmful biochemical signals–inducing chronic inflammation, suppressing the immune system, and accelerating aging in neighboring cells.²

    With cellular senescence as a common link between stress-related diseases, scientists took a closer look to determine whether chronic stress itself functionally increases rates of cellular senescence. In a study, researchers asked 73 adults to self-report their stress levels. Each participant also donated a blood sample that scientists used to measure P16ᴵᴺᴷ⁴ᵃ, a key marker of cellular senescence. Individuals with greater chronic stress exposure showed higher levels of P16ᴵᴺᴷ⁴ᵃ, indicating higher overall levels of cellular senescence.³

    Cellular senescence is associated with cancer, cardiovascular, neurodegenerative and autoimmune disorders. While many of these diseases are age-related, there is some evidence showing that persistent, severe stress can trigger them earlier in a person’s life. This may be due in part to a phenomenon called immunosenescence, senescence in immune cells. When increasing numbers of immune cells become senescent, the body experiences a deterioration in immune response not normally seen in younger people. This can lead to the development and acceleration of two additional aging hallmarks: telomere attrition and chronic inflammation.²

    02 Chronic stress increases inflammaging

    Like stress, inflammation is a normal part of the human experience. It’s the body’s main way of identifying harm–whether from pathogens or injury–and initiating the healing process. Acute, or short-term inflammation, is essential to our health. But when that same inflammation becomes constant, it can actually do more harm than good.⁴

    Chronic inflammation, also known as inflammaging, is age-associated inflammation caused by alterations in the body’s immune response. It’s now understood that these alterations occur when the body’s immune response is disrupted due to immunosenescence. This continuous, systemic inflammation can contribute to the development of several diseases including atherosclerosis, diabetes, and hypertension.

    In addition to its link with stress-induced cellular senescence, inflammaging is also believed to be directly tied to chronic psychological stress by altering levels of cytokines, small proteins that are important in cellular signaling. During the aging process, the body experiences a decrease in anti-inflammatory cytokines, and a simultaneous increase in pro-inflammatory cytokines, leading to overall higher levels of inflammation. Scientists now believe that chronic psychological stress further stimulates pro-inflammatory cytokines. In fact, some studies have shown that antidepressants, which are used to reduce psychological stress, actually reduce enhanced levels of these pro-inflammatory cytokines.²

    This data indicates that living in a constant state of psychological stress can actually accelerate the inflammaging that you might normally experience as a result of the aging process–hastening the cellular damage caused by inflammation so that you actually age more quickly.

    03 Chronic stress induces telomere attrition

    In addition to its effects on cellular senescence and inflammation, research shows that chronic stress can have a structural impact on our chromosomes, tightly packed molecules that house our DNA.

    Telomeres are protective casings located at the end of each chromosome that shield our chromosomes from becoming frayed or tangled. Because our telomeres shorten every time a cell divides, our telomere length naturally shortens with age. Once telomeres become too short, cells experience senescence, cell death, or oncogenic transformations where they can become cancerous. Shorter telomeres have been associated with increased risk for diseases and overall shorter lifespan.⁶

    When we’re young and healthy, telomere attrition is kept at bay with telomerase, an enzyme that replenishes telomere length even as our cells continue to divide. However, chronic stress–and constantly high levels of the stress hormone cortisol–decreases the body’s natural supply of telomerase. This means that chronic stress can actually speed the rate at which we experience telomere attrition, accelerating its systemic aging effects. ⁷

    04 Chronic stress increases oxidative stress

    You know you should be eating a lot of antioxidant-rich fruits and veggies, but do you know why? It’s because antioxidants naturally combat reactive oxygen species (ROS), unstable molecules also known as free radicals that can damage our cells, alter cellular metabolism, and increase inflammation.

    From the time we are born, our cells are constantly managing ROS. But our ability to neutralize ROS can wane as we age, leading to oxidative stress–a phenomenon associated with physical signs of aging. Interestingly, within the body, the main source of ROS is actually our own mitochondria, which become dysfunctional as a result of inflammaging.²

    Our ability to fend off oxidative stress becomes further impaired when we experience a constant state of psychological stress. In a study, scientists compared patients with PTSD to control individuals and discovered that people with PTSD show signs of reduced ROS metabolism. This means that they experience higher rates of oxidative stress. Because oxidative stress itself seems to trigger crosstalk between the immune and central neural systems, scientists believe that stress-induced oxidative stress may actually create a pernicious cycle that further degrades emotional wellbeing, leading to more psychological stress.²

    05 Putting it all together

    Once you dig into the science, it’s easy to see that everything is connected. Increased cellular senescence, inflammaging, telomere attrition, and oxidative stress are all magnified by one another. In short, chronic stress kicks off a cascade of accelerated aging factors that amplify one another, creating system-wide impacts. This underlines the incredibly damaging potential of living a life with unregulated stress levels.

    So how can you help manage chronic stress? In addition to seeking out mental health help from a therapist, experts recommend getting regular exercise, prioritizing sleep, making time for leisure activities and practicing mindfulness. While these tactics may seem mundane in the face of major psychological stress, small daily lifestyle shifts can help the body recover both mentally and physically from a state of chronic stress.¹

    06Key Takeaways

    • Studies have shown that chronic stress speeds the rate at which we age, and increases our risk for numerous age-related diseases.
    • Individuals with chronic stress show higher markers of cellular senescence, a central hallmark of aging tied to cancer, cardiovascular, neurodegenerative and autoimmune disorders.
    • Chronic psychological stress also stimulates pro-inflammatory cytokines and systemic inflammation, a factor linked to several diseases including atherosclerosis, diabetes, and hypertension.
    • Constant exposure to the stress hormone, cortisol, decreases the body’s natural supply of telomerase, an enzyme that prevents telomere attrition, a hallmark of aging linked to diminished lifespan.
    • Higher rates of psychological stress are linked to increased oxidative stress, the overproduction of free radicals that damage our cells and induce inflammation.
    • Regular exercise, prioritizing sleep, making time for leisure activities and practicing mindfulness can help mitigate the psychological and physical impacts of chronic stress.
    References
    [1] https://www.yalemedicine.org/conditions/stress-disorder
    [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400286/
    [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420375
    [4] https://www.ncbi.nlm.nih.gov/books/NBK493173/
    [5] https://www.genome.gov/genetics-glossary/Telomere
    [6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370421/
    [7] https://www.apa.org/monitor/2014/10/

      Reviewed by Alessandra Zonari, PhD, Chief Scientific Officer (CSO) and Co-Founder of OneSkin

      Alessandra earned her Master’s degree in stem cell biology, and her PhD in skin regeneration and tissue engineering at the Federal University of Minas Gerais in Brazil in collaboration with the 3B’s Research Group in Portugal. Alessandra did a second post-doctoral at the University of Coimbra in Portugal. She is a co-inventor of three patents and has published 20 peer-reviewed papers in scientific journals.

      Reviewed by Alessandra Zonari, PhD, Chief Scientific Officer (CSO) and Co-Founder of OneSkin

      Alessandra earned her Master’s degree in stem cell biology, and her PhD in skin regeneration and tissue engineering at the Federal University of Minas Gerais in Brazil in collaboration with the 3B’s Research Group in Portugal. Alessandra did a second post-doctoral at the University of Coimbra in Portugal. She is a co-inventor of three patents and has published 20 peer-reviewed papers in scientific journals.

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