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Ageing and loss of resilience

Researchers have presented results from a recent study exploring associations between ageing and the loss of the ability to recover from stresses.


Ageing in human is a complex and multi-faceted process. It manifests as a progressive functional decline that leads to an increased prevalence of chronic age-related diseases and disease-specific mortality. Most of our understanding about the relationship between ageing and changes in physiological variables comes from cross-sectional studies. These have led to the development of biological clocks that reflect age-related variations in blood markers, DNA methylation patterns or patterns of locomotor activity. However, due to the complexity of ageing it has been difficult to combine the effects of these processes into just one single number.

While many biological clocks have predicted more years of life for those who choose healthier lifestyles, we still do not know how quickly biological age changes over time for the same individual. In particular, how to distinguish between natural fluctuations and genuine changes. This in turn makes it difficult to determine the effects of anti-ageing interventions.

In a recent study, published in Nature Communications, researchers investigated ageing, organism state fluctuation and gradual loss of resilience along individual ageing trajectories. They harnessed data from a large longitudinal database of complete blood count (CBC) measurements. To simplify their analysis, the team used a log-linear mortality estimate from the CBC variables as a single quantitative measure of the ageing process – referred to as dynamic organism state indicator (DOSI).

Loss of resilience

The team found that healthy human subjects were very resilient to stress. Whereas the loss of resilience was related to chronic diseases and elevated all-cause mortality risks. In addition, the rate of recovery to the baseline after stresses deteriorated with age.

Across the average population, it took 2 weeks for 40-year-old healthy adults to recover, but this stretched to 6 weeks for 80-year-old adults. The team confirmed these findings in two different datasets based on both blood test parameters and physical activity levels recorded by wearable devices. The team highlighted that if the trend were to be consistent in later years, extrapolation shows a complete loss of resilience at around 120-150 years old. Reduced resilience was also observed in individuals not suffering from major chronic disease. This may explain why we do not see an increase of maximum lifespan while the average lifespan steadily grows. As a result, it is clear that without preventing the root cause of the underlying loss of resilience you cannot effectively increase maximum lifespan.

Professor Andrei Gudkov, co-author, stated:

“This work, in my opinion, is a conceptual breakthrough because it determines and separates the roles of fundamental factors in human longevity – the aging, defined as progressive loss of resilience, and age-related diseases, as ‘executors of death’ following the loss of resilience. It explains why even most effective prevention and treatment of age-related diseases could only improve the average but not the maximal lifespan unless true antiaging therapies have been developed.”

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