Telomeres and the natural lifespan limit in humans.

Troels Steenstrup,Gerald S Berenson,Ronit Sinnreich,Lene Christiansen,Jeremy D Kark,Carlos Labat,Simon Verhulst,Timothy D Spector,Daniel Levy,Steven C Hunt,Sharon A Savage,Konstantin G Arbeev,Kirsten Ohm Kyvik,Mikael Thinggaard,Abraham Aviv,Kaare Christensen,Wei Chen,Giuseppe Paolisso,Massimo Mangino,Michelangela Barbieri,Annette L Fitzpatrick,Masayuki Kimura,Inge Petersen,Christine Dalgård,Shahinaz M Gadalla,Anatoliy I Yashin,Athanase Bénétos ,Shih Jen Hwang ,Jacob Hjelmborg

doi:10.18632/aging.101216

Abstract

An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal natural lifespan limit. We define leukocyte telomere length of 5 kb as the ‘telomeric brink’, which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus, secular trends in life expectancy should confront a biological limit due to crossing the telomeric brink.

Highlights

Cardiovascular disease (CVD), principally due to atherosclerosis, remains the largest cause of death and influences longevity in the US [1,2]
We examined the potential role of telomere length in human longevity in two settings: contemporary life expectancy, and life expectancy of 100 years (LE-100) i.e., assuming survival until the age of 100 years [17]
Our analysis suggests that the individual’s leukocyte telomere length (LTL), as reflected in his/her ranking, may be a major determinant of that individual’s natural lifespan limit from the standpoint of telomere biology

Summary

Introduction

Cardiovascular disease (CVD), principally due to atherosclerosis, remains the largest cause of death and influences longevity in the US [1,2]. Coupled with observations that LTL, which reflects telomere length in somatic tissues [13], is highly heritable [14,15] and is largely determined at birth [16], these findings suggest that telomere length might play an active role in CVD and longevity. Such a conclusion is relevant to the debate about the existence of a natural lifespan limit for humans [17,18,19,20,21]. We show that with predicted upward trajectories of life expectancy, the proportion of these individuals will only increase in the general population

Methods

Results

Conclusion