Biomarkers used to track benefits of anti-aging therapies can be misleading, suggests nematode study: Markers of ‘biological age’ can change without turning a ‘fast ager’ into a ‘slow ager’

We all grow old and die, but we still don’t know why. Diet, exercise and stress all effect our lifespan, but the underlying processes that drive ageing remain a mystery. Often, we measure age by counting our years since birth and yet our cells know nothing of chronological time — our organs and tissues may age more rapidly or slowly regardless of what we’d expect from counting the number of orbits we tale around the sun.

For this reason, many scientists search to develop methods to measure the “biological age” of our cells — which can be different from our chronological age. In theory, such biomarkers of ageing could provide a measure of health that could revolutionize how we practice medicine. Individuals could use a biomarker of ageing to track their biological age over time and measure the effect of diet, exercise, and drugs and predict their effects to extend lifespan or improve quality of life. Medicines could be designed and identified based on their effect on biological age. In other words, we could start to treat ageing itself.

However, no accurate and highly predictive test for biological age has been validated to date. In part, this is because we still don’t know what causes ageing and so can’t measure it. Definitive progress in the field will require validating biomarkers throughout a patient’s lifetime, an impractical feat given human life expectancy.

To understand the irreducible components of ageing, and how these can be measured and tested, researchers turn to laboratory animals. Unlike humans, the nematode C. elegans lives for an average of two weeks, making it easier to collect behavioural and lifespan data that would otherwise require centuries.

The nematode C. elegans begin adulthood vigorously exploring their environment. Over time, they slow and stop crawling, a behavioural stage known as vigorous movement cessation (VMC). VMC is a biomarker of ageing and a proxy for nematode health. Studies of genetically identical nematodes have shown it is a powerful predictor of a worm’s lifespan, but at the same time, interventions designed to alter ageing can disproportionately affect VMC in comparison to lifespan and vice versa. Researchers at the Centre for Genomic Regulation (CRG) in Barcelona seek to understand why this happens and what this means for the ageing process in humans.

A team lead by Dr. Nicholas Stroustrup, Group Leader at the CRG’s Systems Biology research programme, has developed the ‘Lifespan Machine’, a device that can follow the life and death of tens of thousands of nematodes at once. The worms live in a petri dish under the watchful eye of a scanner that monitors their entire lives. By imaging the nematodes once per hour for months, the device gathers data at unprecedented statistical resolution and scale.

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