Dr Richard Siow on measuring healthy ageing: Biomarkers, DNA methylation, and happiness

Scientists are revealing how molecular pathways associated with healthy ageing can be activated or deactivated by nutrients – an exciting development in the science of longevity But we mustn’t lose sight of the bigger picture, says Dr Richard Siow, who argues that healthy ageing is as much about emotional wellbeing as it is DNA methylation patterns

“There are many, many different markers that you might want to put in place to build a picture of [...] the holistic view of wellness,” said Richard Siow, whose long CV indicates the clout he has in the field of longevity research.

Siow is director of ageing research at King’s College London; visiting senior academic at the University of Oxford; chief editor of Frontiers in Ageing; advisory board member of The Lancet Healthy Longevity; and scientific advisor to numerous health companies.

Possible biomarkers could be the level of stress hormones like cortisol in the blood; sleep quality and quantity; someone’s hand grip strength; or even how much someone feels happy, in addition to levels of glucose and cholesterol that are more routinely measured.

DNA methylation patterns are also increasingly understood as important biomarkers for health ageing. In fact, they are “our biological ageing clocks”, said Siow.

DNA methylation is a process by which genes are regulated over time. Like the microbiome, methylation patterns change throughout life and are impacted by diet, sleep patterns, exercise, stress and lifestyle. If someone’s methylation pattern resembles that of a younger person, this suggests a healthy ageing trajectory.

Although the research is still in the early stages, one exciting development in the field of healthy ageing research is the growing understanding of how molecular pathways associated with longevity can be activated or deactivated, including through nutraceuticals, said Siow.

“[...] You might consider [this] as longevity-enhancing pathways at the cellular level. There’s currently much research in worms, flies, mice, and model organisms, but we need to learn more about people in the context of lifestyle.

“Our wellness trajectory isn’t based only on our genetics and our DNA profile. That’s important, but [it’s] also how certain genes are switched on and switched off, and we can monitor that in many different ways to look at the DNA being activated or silenced,” said Siow.

Using nutrients to ‘downregulate’ specific genes

An individual, for instance, may have genes that increase inflammation in the body. Scientists are investigating ways to “switch off” or downregulate these genes in order to reduce inflammation. Noting that the real-life applications of the research were “still lacking in some respects”, Siow asked:

“What are the nutrients that may downregulate it? What is the genetic profile for the individual and are they at higher risk of inflammation because they have certain genes that can be more readily switched on?”

Some individuals may not have the relevant molecular pathway that metabolises a nutrient into an active compound “switched on”, which means the nutrient won’t be beneficial for the individual.

Personal wellness: Putting the science into perspective

While nutrition is undoubtedly a fundamental component of healthy ageing, Siow was reluctant to pick out certain nutrients that benefit longevity, instead preferring more holistic recommendations.

“Perhaps the research has shown that in [mice] you can extend lifespan if you caloric restrict, and so on. But you’re not considering the psychological well-being of that poor mouse that you’re not feeding,” he said.

“Or you may be super anxious that you are taking all of these supplements, and you’re looking at all of your fitness trackers at the same time, and you’re paranoid that you’ve not done 9,999 steps. Those kinds of things don’t help your psychological wellbeing.”

Psychological wellbeing is therefore of key importance to healthy ageing. And while pursuing personal wellbeing can mean different things for different people – it doesn’t have to mean meditating every day for 30 minutes, Siow said – it should ideally take place within the general limits of what constitutes a healthy diet and lifestyle. Some people may say their emotional wellbeing is fulfilled by watching TV all day, staying up late, and eating fast food – but this is not the foundation for good physical or mental health.

Siow emphasised that there was a role for nutrient supplementation and nutraceuticals in healthy ageing, but said it was important to “put personal lifestyle in perspective”.

“The nutraceutical companies are trying to say: ‘This will extend your lifespan, or this will activate the mTORsirtuin axis or the AMP kinase, and your stem cells are going to be jumping for joy.’ But are you going be happier? No,” he said.

“It’s about mindset [...] and being aware about the stresses of the workplace and so on. It’s really important that we consider how a healthy diet, which may or may not include supplements, can also lead to psychological wellbeing.”

Tracking health in real time

Nevertheless, a growing understanding of key biomarkers associated with healthy ageing and developing accurate metrics and methods to measure them could allow people to be aware of their own personal longevity trajectory.

Such metrics would allow people to track their health regularly throughout their lives so that they reach an older age whilst remaining in optimal health, rather than living with multiple age-related health conditions as is so often the case today.

“[We need] more public health education, more societal interventions, more awareness of the value of health tracking, more translational and clinical research, and more funding for these kinds of areas, because global populations are living longer, but not necessarily healthier,” Siow said.

Covid-19: A ‘ground-breaking’ influence on proactive health

Finally, the healthy ageing category is evolving not just through scientific research and tech advances: social dynamics and the public mindset towards healthy ageing are also changing.

The impact of the Covid-19 pandemic has had a “ground-breaking” influence on people’s awareness of personal health and willingness to test regularly to reduce the risk and severity of illness and, if necessary, taking action such as hand washing, social distancing and acceptance of vaccination at both an individual and population level, Siow said.

“The willingness to be tested – understanding that necessity to reduce the risk and severity of illness as we age – [...] is an important concept that we have all been educated about. That, I believe, will drive the future mindset for healthy ageing, health in general, and wellness,” he added.