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Longevity
3.3.2024

The signs of the times: How human organs age differently

A look at the different aging processes and their effects on our health

Kace Rodriguez

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Age is complex and cannot be expressed in a single number. Two people of the same age can be very different — one healthy, the other ill or with chronic conditions. Even within the human body, age cannot be uniform. Some parts of the body can be healthy and functional for a long time, while other organs are already on the verge of failure. Experts say the ovaries age so fast that women in their thirties are already geriatric.

A good comparison is that between the human body and a car — both need careful care. If a car's paint isn't scratched, it can last for decades. An engine can run for a lifetime if it is regularly well maintained. Brake pads wear out very quickly and tires should be changed every few years, but a new clutch may not be needed until mid-term years. The service booklet and displays on the dashboard remind you of the next service.

In the future, similar to cars, there could also be a “control dashboard” for human health, which provides us with important health data and maintenance plans. Experts are working to develop such technologies to better monitor and maintain our health.

Clocks to measure the aging process

When scientist Steve Horvath presented his so-called Horvath watch, it was a step in that direction. The watch is a tool for measuring biological aging based on epigenetics, i.e. the changing methylation patterns and other types of DNA modifications that change with age. The concept of his watch is based on the fact that DNA methylation patterns change as we age. These epigenetic patterns correlate with the aging process and can serve as biomarkers for estimating biological age — i.e. a better measure of how fast we age than chronological age.

Since Horvath presented the first multi-system watch in 2013, there has been a race for more efficient methods to quantify the rate and effects of aging on the human body. In a study from 2022, several biomarkers were used to prove that different parts of the human body age at different rates at a cellular level. A study of healthy adults has shown that the turnover rates of certain human cell types, from which the lifespan of the cells can be derived, range from 2 days for a type of white blood cell to 90 years for nerve cells.

Scientists disagree on the best way to measure the biological aging of organs. And despite ongoing research, there is no published, validated, system-specific epigenetic clock. A group of researchers from the University of Melbourne has now developed a kind of new biological clock for aging that is not based on epigenetic measurements.

A new way to fight disease?

“The aging of one body system, an organ system, can selectively strongly influence the aging of other systems,” says Andrew Zalesky, a neuroscientist at the University of Melbourne. He and a team of scientists have taken this system-oriented measurement of biological age a step further in a study recently published in Nature Medicine. By mapping the selective effects of aging organs at different rates, they created a new way to quantify and possibly combat the age-related risk of chronic diseases.

The researchers also found links between the rate of organ-specific aging and lifestyle, as well as demographic factors such as proximity to green spaces, which tend to be associated with a “younger” lung. They also found causal relationships between organ-specific aging rates. For example, lung aging can lead to a higher rate of heart aging, which in turn can affect the aging rate of other body systems.

Instead of relying on epigenetic aging clocks to measure biological age, the scientists from Melbourne derived their “clock” from the British Biobank, an extensive data set that has collected the genetic and health data of 500,000 people since 2006. In their latest study, scientists developed a new measure of biological age based on data from brain scans and physiological phenotypes or characteristics. Using data from healthy adults, they trained machine learning models to predict the age of various body parts. By comparing this age with chronological age, the model was able to identify whether, for example, the heart, lungs, or kidneys were older or younger than typical for a specific age. This gap was used to derive organ-specific methods for measuring biological age in seven body and three brain systems.

Each year that the heart ages biologically, the brain age increases by 27 days.

For example, the researchers found links between the aging of the heart and the brain. Each year that the heart ages biologically, the brain age increases by 27 days. The researchers also found links between the biological age of various systems and 16 chronic diseases, including osteoarthritis, diabetes, and cancer. While these correlations do not show that a particular disease or lifestyle factor causes an organ to age or vice versa, they could be useful for deciphering the complex interactions between these body systems.

The real challenge is moving from a fragmented approach to healthcare — one doctor per organ — to a redefinition of health as a dynamic network of interactions between tissues and organ systems. This means that doctors could focus on specific organs that age faster than the systems surrounding them, potentially slowing down aging or halting disease. A better understanding of biological age variations could also help doctors develop therapies for people based on their individual risk factors.

To stick with the comparison with a car: As the car gets older, everything is subject to wear and tear. When does the exhaust or other critical part need to be replaced if there are signs that something is about to go wrong? An accurate and affordable biological aging test is the ace of the mechanic, who recognizes that the air-fuel mixture isn't right even before you notice a strange smell. Fixing this issue would reduce fuel consumption, make the car smoother, and prevent engine wear. Without a good mechanic (or an accurate, affordable aging watch), we might not realize that something is wrong until it's too late or too expensive to fix it. But which aging measurement, which “mechanic” can you really trust?

References

  1. Never, C., Li, Y., Li, R., Yan, Y., Zhang, D., Li, T., Li, Z., Sun, Y., Ding, J., Wan, Z., Gong, J., Shi, Y., Huang, Z., Wu, Y., Cai, K., Zong, Y., Wang, R., Xu, X (2022). Distinct biological ages of organs and systems identified from a multi-omics study. Cell Reports, 38(10), 110459. https://doi.org/10.1016/j.celrep.2022.110459
  2. Seim, I., Ma, S. & Gladyshev, V.N. (2016). Gene Expression Signatures of Human Cell and Tissue Longevity. Research Gate, 2(1). https://doi.org/10.1038/npjamd.2016.14
  3. Tian, Y.E., Cropley, V., Maier, A.B., Lautenschlager, N.T., Breakspear, M. & Zalesky, A. (2023). Heterogeneous aging across multiple organ systems and prediction of chronic disease and mortality. Nature Medicine, 29(5), 1221—1231. https://doi.org/10.1038/s41591-023-02296-6

Scientific Terms

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Glossary

Age is complex and cannot be expressed in a single number. Two people of the same age can be very different — one healthy, the other ill or with chronic conditions. Even within the human body, age cannot be uniform. Some parts of the body can be healthy and functional for a long time, while other organs are already on the verge of failure. Experts say the ovaries age so fast that women in their thirties are already geriatric.

A good comparison is that between the human body and a car — both need careful care. If a car's paint isn't scratched, it can last for decades. An engine can run for a lifetime if it is regularly well maintained. Brake pads wear out very quickly and tires should be changed every few years, but a new clutch may not be needed until mid-term years. The service booklet and displays on the dashboard remind you of the next service.

In the future, similar to cars, there could also be a “control dashboard” for human health, which provides us with important health data and maintenance plans. Experts are working to develop such technologies to better monitor and maintain our health.

Clocks to measure the aging process

When scientist Steve Horvath presented his so-called Horvath watch, it was a step in that direction. The watch is a tool for measuring biological aging based on epigenetics, i.e. the changing methylation patterns and other types of DNA modifications that change with age. The concept of his watch is based on the fact that DNA methylation patterns change as we age. These epigenetic patterns correlate with the aging process and can serve as biomarkers for estimating biological age — i.e. a better measure of how fast we age than chronological age.

Since Horvath presented the first multi-system watch in 2013, there has been a race for more efficient methods to quantify the rate and effects of aging on the human body. In a study from 2022, several biomarkers were used to prove that different parts of the human body age at different rates at a cellular level. A study of healthy adults has shown that the turnover rates of certain human cell types, from which the lifespan of the cells can be derived, range from 2 days for a type of white blood cell to 90 years for nerve cells.

Scientists disagree on the best way to measure the biological aging of organs. And despite ongoing research, there is no published, validated, system-specific epigenetic clock. A group of researchers from the University of Melbourne has now developed a kind of new biological clock for aging that is not based on epigenetic measurements.

A new way to fight disease?

“The aging of one body system, an organ system, can selectively strongly influence the aging of other systems,” says Andrew Zalesky, a neuroscientist at the University of Melbourne. He and a team of scientists have taken this system-oriented measurement of biological age a step further in a study recently published in Nature Medicine. By mapping the selective effects of aging organs at different rates, they created a new way to quantify and possibly combat the age-related risk of chronic diseases.

The researchers also found links between the rate of organ-specific aging and lifestyle, as well as demographic factors such as proximity to green spaces, which tend to be associated with a “younger” lung. They also found causal relationships between organ-specific aging rates. For example, lung aging can lead to a higher rate of heart aging, which in turn can affect the aging rate of other body systems.

Instead of relying on epigenetic aging clocks to measure biological age, the scientists from Melbourne derived their “clock” from the British Biobank, an extensive data set that has collected the genetic and health data of 500,000 people since 2006. In their latest study, scientists developed a new measure of biological age based on data from brain scans and physiological phenotypes or characteristics. Using data from healthy adults, they trained machine learning models to predict the age of various body parts. By comparing this age with chronological age, the model was able to identify whether, for example, the heart, lungs, or kidneys were older or younger than typical for a specific age. This gap was used to derive organ-specific methods for measuring biological age in seven body and three brain systems.

Each year that the heart ages biologically, the brain age increases by 27 days.

For example, the researchers found links between the aging of the heart and the brain. Each year that the heart ages biologically, the brain age increases by 27 days. The researchers also found links between the biological age of various systems and 16 chronic diseases, including osteoarthritis, diabetes, and cancer. While these correlations do not show that a particular disease or lifestyle factor causes an organ to age or vice versa, they could be useful for deciphering the complex interactions between these body systems.

The real challenge is moving from a fragmented approach to healthcare — one doctor per organ — to a redefinition of health as a dynamic network of interactions between tissues and organ systems. This means that doctors could focus on specific organs that age faster than the systems surrounding them, potentially slowing down aging or halting disease. A better understanding of biological age variations could also help doctors develop therapies for people based on their individual risk factors.

To stick with the comparison with a car: As the car gets older, everything is subject to wear and tear. When does the exhaust or other critical part need to be replaced if there are signs that something is about to go wrong? An accurate and affordable biological aging test is the ace of the mechanic, who recognizes that the air-fuel mixture isn't right even before you notice a strange smell. Fixing this issue would reduce fuel consumption, make the car smoother, and prevent engine wear. Without a good mechanic (or an accurate, affordable aging watch), we might not realize that something is wrong until it's too late or too expensive to fix it. But which aging measurement, which “mechanic” can you really trust?

Referenzen

  1. Never, C., Li, Y., Li, R., Yan, Y., Zhang, D., Li, T., Li, Z., Sun, Y., Ding, J., Wan, Z., Gong, J., Shi, Y., Huang, Z., Wu, Y., Cai, K., Zong, Y., Wang, R., Xu, X (2022). Distinct biological ages of organs and systems identified from a multi-omics study. Cell Reports, 38(10), 110459. https://doi.org/10.1016/j.celrep.2022.110459
  2. Seim, I., Ma, S. & Gladyshev, V.N. (2016). Gene Expression Signatures of Human Cell and Tissue Longevity. Research Gate, 2(1). https://doi.org/10.1038/npjamd.2016.14
  3. Tian, Y.E., Cropley, V., Maier, A.B., Lautenschlager, N.T., Breakspear, M. & Zalesky, A. (2023). Heterogeneous aging across multiple organ systems and prediction of chronic disease and mortality. Nature Medicine, 29(5), 1221—1231. https://doi.org/10.1038/s41591-023-02296-6

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