The Ups and Downs of Ageing: It's Not a Straight Line

Image credit: https://openai.com/index/dall-e/

We all know that getting older brings changes, but it turns out that these changes aren't as straightforward as we might think. It's not just a case of a slow, steady decline. A recent study looked at how different molecules in our bodies change as we age, and it revealed some fascinating insights. This wasn't just a quick look; it followed 108 people over several years, tracking changes in their blood, gut, skin, mouth, and nose.

More than just a gradual decline

For a long time, scientists thought that many age-related changes happened in a linear way – a bit like a gentle slope downwards. However, this new study shows that this isn’t quite right. In fact, most of the changes observed were nonlinear, meaning they speed up or slow down at different points in our lives. Think of it like a rollercoaster with ups and downs rather than a gentle slide.

Key turning points in life
The study found two major periods where big changes happen. These are around 44 years old and 60 years old. These aren't necessarily when we suddenly feel 'old', but when the molecules in our body show significant shifts.

• Around 44, there appear to be noticeable changes in areas like cardiovascular health, and how our bodies handle fats and alcohol.

• Then, around 60, the focus shifts to things like how our immune system works and how we process sugars.

These changes aren't just random; they seem to be linked to an increased risk of certain diseases as we get older.

How scientists tracked these changes
The researchers collected various samples from the participants: blood, stool, skin, oral and nasal swabs. They then analyzed these samples using advanced techniques to measure different types of molecules:

• Transcriptomics: This looks at RNA, which carries the instructions for making proteins.

• Proteomics: This looks at proteins, which are the workhorses of our cells.

• Metabolomics: This looks at metabolites, which are the small molecules that our body uses and produces.

• Cytokines: These are proteins that signal between cells, especially in the immune system.

• Lipidomics: This focuses on fats and other lipids.

• Microbiome: This refers to the communities of bacteria that live in our gut, skin, mouth and nose.

• Clinical lab tests: These are routine tests done on blood, such as cholesterol and glucose.

By looking at all these different aspects, the researchers could build up a detailed picture of how ageing affects our bodies.

Nonlinear patterns and what they mean
The researchers used advanced statistical methods to show that the changes observed were not linear. They found that most of the molecules they measured changed in a nonlinear way. This means that the rate of change wasn't constant; it accelerated at certain times of life and slowed down at others.
To understand these nonlinear patterns, they grouped molecules with similar change patterns into clusters. Some of these clusters showed clear trends:

• Some molecules remained stable until about 60, then decreased quickly.

• Others fluctuated before 60, then sharply increased after.

It’s like some things in our bodies have a slow burn until around 60, then accelerate.

What the findings mean for health
The nonlinear changes in molecules have significant implications for disease risk. For example, the study found that:

• Cardiovascular disease risk increases significantly after 60, linked to changes in blood clotting and fat metabolism.

• Kidney function declines nonlinearly with age.

• Type 2 diabetes risk escalates, especially after 60.

• Oxidative stress, linked to inflammation, significantly increases after 60.

• The body's ability to repair DNA appears to increase before 50, then decline between 50 and 56.

• The health of skin and muscle also declines faster around the age of 40 and 60.

These findings suggest that our risk of disease doesn't just increase gradually; it can spike at different points as we age.

Waves of change
The researchers also looked at how molecular changes seem to happen in "waves", with two notable peaks, one around 44 and the other around 60 years of age. This approach identified changes that might be missed by simply looking at linear changes over time. These waves represent periods where a large number of molecules change together, which may reflect major shifts in the body's biology.

• The first wave around 44 was linked to changes in lipid and alcohol metabolism.

• The second wave around 60 was connected to immune function and how the body uses sugars.

What this means for the future
This study is exciting because it shows us that the ageing process isn't as simple as we thought. By understanding these nonlinear changes, and the specific periods of change in our lives, we may be able to develop strategies to slow down the ageing process and to identify at-risk people earlier.

Limitations of the study It is important to note that the study had some limitations:

• The sample size of 108 participants is considered relatively small for deep learning applications, which may have affected the results.

• The participants were mainly from the community around Stanford University, which might limit how broadly the results apply.

• The observation period for the participants was a median of 1.7 years, which may not be long enough to capture long-term ageing patterns.

In conclusion
Ageing is a complex process with ups and downs, rather than a simple, steady decline. This research highlights the need to consider nonlinear changes in molecules and it suggests that specific periods in our lives are more important than others when it comes to age-related changes. This study lays the groundwork for future studies to investigate what can be done to promote healthy ageing and reduce the risk of age-related diseases.
 

Journal information: Nonlinear dynamics of multi-omics profiles during human aging. Nature Ageing (2024).  https://doi.org/10.1038/s43587-024-00692-2

Additional information: https://www.nature.com/nataging