Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism.

S W Jansen,H Pijl,C M Cobbaert,R G J Westendorp,B E Ballieux,P E Slagboom,B A Demeneix,E Van Der Spoel,D Van Heemst,J Van Der Grond,A A Akintola,P Egri,F Roelfsema,B Gereben,C Fekete,Z Kvarta-Papp

doi:10.1038/srep11525

Abstract

Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis may favour longevity without altering energy metabolism.

Highlights

Mortality rate, a lower prevalence of diabetes and cardiovascular disease[3] and are well suited for studying the mechanisms underlying healthy human longevity
We found that when nonagenarians were stratified for their propensity to reach advanced age, those with the lowest family mortality history score had the highest TSH levels and slightly lower levels of free T4 and free T37
We investigated if human longevity is associated with differences in TSH and/or TH and whether these concur with differences in energy metabolism because this process is responsive to TSH/ TH action and has been associated with longevity in model organisms

Summary

Introduction

Mortality rate, a lower prevalence of diabetes and cardiovascular disease[3] and are well suited for studying the mechanisms underlying healthy human longevity. The mechanistically linked “free radical theory of ageing” proposes that free radicals generated as by-products of oxidative metabolism underpin the negative correlation between lifespan and resting metabolic rate[5]. We found that when nonagenarians were stratified for their propensity to reach advanced age, those with the lowest family mortality history score had the highest TSH levels and slightly lower levels of free T4 (fT4) and free T3 (fT3)[7]. Studies in the oldest old from the general population link increased levels of TSH with reduced old age mortality[10]. We investigated whether such differences in TSH and/or TH concur with differences in energy metabolism, a physiological process that has been associated with longevity in model organisms and is known to be responsive to TSH/TH action

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