Endocrine Abstracts

Several differences have been observed in thyroid function parameters between older and younger individuals. Notably, circulating thyroid stimulating hormone (TSH) levels gradually increase with age, a shift shown to extend to extremely high ages. While clinically abnormal thyroid function parameters have been consistently associated with ill health, the mechanisms underlying mild age-related variations in circulating levels of TSH and thyroid hormones and their health consequences remain poorly understood, especially at advances ages.

Although ageing is universally driven by deterioration of biological integrity over time, it manifests itself in different individuals at a different pace and by different (tissue-specific) pathologies. The heterogeneity and complexity of the ageing process impose specific challenges for studies on age-related hormonal changes. Theoretically, mild age-related differences in thyroid function parameters might be indicative of (i) subclinical thyroid disease, (ii) adaptive hormonal responses to underlying disease(s), or (iii) selective survival of individuals genetically predisposed to higher TSH levels.

In order to identify determinants of human longevity, the Leiden Longevity Study (LLS) included 421 families with at least two long-lived Caucasian siblings fulfilling the age criteria (men ≥89 years and women ≥91 years) without selection on health or demographics. We also included the offspring of these long-lived siblings and partners thereof, serving as a control group. In a subsample of offspring and controls, blood was frequently sampled over 24 hours, from which circulating TSH levels were measured every 10 minutes and levels of thyroid hormones every hour. Previously, we found higher TSH secretion and a stronger TSH-fT3 temporal relationship in the offspring compared to controls. Our current research which is performed in the THYRAGE (Resetting the THYRoid axis for prevention of AGE-related diseases and co-morbidities) consortium is devoted at disentangling what mechanism(s) underlie the observed differences in thyroid function parameters and how these might favour longevity.