Older white man, with white hair holding the hand of an unseen female healthcare worker with a stethoscope around her neck - image to represent impact of male hormone on aging health
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Research led by the University of Nottingham shows that levels of a type of hormone produced by the testes at puberty can predict a man’s health status in later life.

Insulin-like peptide 3 (INSL3) is produced by mature Leydig cells, which also produce testosterone, in the testes during puberty.

Unlike testosterone, INSL3 levels stay largely the same throughout life after increasing until the age of 18-20 years, reaching an average personal level for many years and then showing a slight decline with aging of about 15 percent per year from the age of 40 onwards. This means if a man’s levels are low at the age of 20, they will remain low throughout their life.

The known association with aging makes INSL3 an interesting biomarker, but specific links with health were previously unclear. To investigate further, Ravinder Anand-Ivell, a professor at the University of Nottingham, and colleagues analyzed whether INSL3 levels were linked with age-related illness in a cohort of 3000 men aged 40-79 years on recruitment.

“The holy grail of aging research is to reduce the fitness gap that appears as people age. 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,” commented Anand-Ivell, who co-led the research, in a press statement.

Writing in the journal Frontiers in Endocrinology, the authors report that the level of INSL3 in the blood of the men in the study varied widely and up to 10-fold differences in levels between individuals were observed. INSL3 levels were associated with several age-related illnesses, such as bone weakness, sexual dysfunction, diabetes, and cardiovascular disease.

Low INSL3 was associated with increased risk for seven out of nine comorbidities including cancer, diabetes, cardiovascular disease and low bone density in older age. The team also found a link between high levels of INSL3 and cardiovascular disease and hypertension.

“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,” said first-author Richard Ivell, also a professor at 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.”

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