02 January 2023 By DAVID NIELD
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A variety of age-related illnesses – including bone weakness, sexual dysfunction, diabetes, cancer, and cardiovascular disease – can be predicted by a single hormone that appears at a steady level in men across the course of their lives, new research reveals.
That hormone is INSL3, and it first appears during puberty. From then on, its levels only dip slightly in old age. This consistency and the early age at which it appears makes INSL3 valuable to scientists – and possibly men’s health.
Someone with lower INSL3 levels at a young age is probably going to have lower levels of the hormone in old age too, the new research shows. If that translates to a greater risk of health complications, as the study suggests may be the case, those health risks could potentially be managed many years earlier.
“Understanding why some people are more likely to develop disability and disease as they age is vital so that interventions can be found to ensure people not only live a long life but also a healthy life as they age,” says reproductive endocrinologist Ravinder Anand-Ivell from the University of Nottingham in the UK.
“Our hormone discovery is an important step in understanding this and will pave the way for not only helping people individually but also helping to ease the care crisis we face as a society.”
INSL3 is made by the same cells in the testes that produce testosterone; unlike testosterone, INSL3 doesn’t fluctuate as men become adults.
To monitor the level of INSL3 in the blood, researchers took samples from more than 2,200 men across eight different regional centers in Europe. The men’s INSL3 levels stayed steady over time and also varied significantly between individuals, enough to tease apart health risks.
Researchers suggest that INSL3 levels in the blood reliably correlate to the number and health of the Leydig cells in the testes – having fewer of these cells and less testosterone has also been linked to numerous health issues in later life.
“Now we know the important role this hormone plays in predicting disease and how it varies amongst men, we are turning our attention to finding out what factors have the most influence on the level of INSL3 in the blood,” says molecular endocrinologist Richard Ivell from the University of Nottingham.
“Preliminary work suggests early life nutrition may play a role, but many other factors such as genetics or exposure to some environmental endocrine disruptors may play a part.”
Across nine morbidity categories that participants reported in questionnaires, including cancer, diabetes, and cardiovascular disease, INSL3 was linked to an increased risk of morbidity in eight of them (only depression wasn’t found to have any correlation in this study).
But when the researchers adjusted for other hormonal and lifestyle factors, such as BMI and smoking status, most of these associations with INSL3 were lost, except for high blood pressure and cardiovascular disease.
And testing whether INSL3 levels in blood samples from a subset of men could foreshadow health outcomes roughly four years later, lower hormone levels were associated with seven of the nine comorbidity categories. But again, this was without taking into account other factors.
One area the scientists are keen to explore in future studies is how INSL3 relates to sexual health, with its strong association with testosterone, but that wasn’t included in detail in this particular piece of research.
Future studies should also “focus on longer time periods to determine whether INSL3 measured in younger or middle-aged men… is truly predictive of the later appearance of age-dependent health issue,” the researchers conclude.
If the link between INSL3 and these health risks is established by further studies, and scientists are able to pinpoint exactly why the link exists, it means preparations can be made much earlier to try and spot – and stop – a variety of age-related health problems from happening.
“The holy grail of aging research is to reduce the fitness gap that appears as people age,” says Anand-Ivell.
The research has been published in Frontiers in Endocrinology.
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