Insulin-like peptide 3 (INSL3) is a constitutive hormone secreted in men by the mature Leydig cells of the testes, explained the authors of the new study, published in Frontiers in Endocrinology.
“It is an accurate biomarker for Leydig cell functional capacity, reflecting their total cell number and differentiation status,” they said.
“The holy grail of aging research is to reduce the fitness gap that appears as people age,” said Ravinder Anand-Ivell, PhD, associate professor in endocrinology and reproductive physiology at the University of Nottingham (England), and study coauthor. 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, she highlighted.
The European team of researchers, led by scientists from the University of Nottingham, set out to determine the ability of INSL3 as a biomarker to predict hypogonadism and age-related morbidity, and whether this also allowed it to predict morbidity in a similar way to testosterone.
For the study, the researchers analyzed blood samples from the European Male Aging Study (EMAS) cohort to assess circulating INSL3 and its cross-sectional and longitudinal relationships to hypogonadism – defined by testosterone less than 10.5 nmol/L – and a range of age-related morbidities determined by correlation and regression analysis.
The EMAS cohort of community-dwelling men comprises more than 3,000 men, aged 40-79 years at the time of recruitment, from eight centers in Europe. Men were recruited from 2003 to 2004 and again 4-5 years later for a second phase of the study. In both phases, blood was collected for hormonal measurements, and subjects were assessed for anthropometric parameters and asked to complete questionnaires relating to their health, lifestyle, and diet.
Hormone levels remain constant
The results showed that, unlike testosterone, which fluctuates throughout a man’s life, INSL3 remains consistent, with the level at puberty remaining largely the same throughout a man’s life, decreasing only slightly into old age. “This makes it the first clear and reliable predictive biomarker of age-related morbidity as compared with any other measurable parameters,” explained the researchers.
They also discovered that the level of INSL3 in blood “correlates with a range of age-related conditions,” such as bone weakness, sexual dysfunction, diabetes, and cardiovascular disease.
They emphasized that the discovery of the consistent nature of this hormone is “very significant.” It means that a man with high INSL3 when young will still have high INSL3 when he is older, but someone with low INSL3 already at a young age will have low INSL3 when older, “making him more likely to acquire typical age-related illnesses.”
Dr. Anand-Ivell commented that the hormone discovery was an “important step” and will pave the way for not only helping people individually but also helping to “ease the care crisis we face as a society.”
Exciting possibilities for predicting age
The study also showed that the normal male population, even when young and relatively healthy, still shows an almost 10-fold variation between individuals in the concentration of INSL3 in the blood, the authors reported.
The authors highlighted that the study’s strengths are the large and comprehensive dataset provided by the EMAS cohort, together with the accuracy of the hormonal parameters measured. The weaknesses, they explained, are the self-reported nature of some of the morbidity parameters as well as the relatively short longitudinal dimension of only 4.3 years average.
Richard Ivell, University of Nottingham, and lead author, explained that now the important role of INSL3 in predicting disease, and how it varies amongst men, had been established, the team is looking to investigate what factors have the most influence on the level of INSL3 in the blood. “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”.
The study findings open up “exciting possibilities for predicting age-related illnesses and finding ways to prevent the onset of these diseases with early intervention,” the authors enthused.
The study was initiated and supported by the European 5th Framework, and the German Research Council provided funding for the INSL3 analysis. The authors declared no conflicts of interest.
Dr. Hicks has disclosed no relevant financial relationships. A version of this article first appeared on MedscapeUK.