Telomeres and the natural lifespan limit in humans

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.

Keywords: leukocytes; life-expectancy; longevity; maximal lifespan; sex.

Figure 1

Scatter plots and density plots of LTL as a function of age for males and females residing in different countries. Measurements of LTL were performed in the same laboratory on DNA donated by participants in different studies in different countries (Supplemental Table 1). The horizontal dashed lines in the top panels and vertical dashed lines in the bottom panels indicate LTL values of 5 kb. The bottom plots are smoothed histograms obtained by kernel density estimation.

Figure 2

Predicted proportion of the composite study population reaching the telomere brink (TB; 5 kb) based on period life table mortality (period), life expectancy of 100 years (LE-100) and LTL attrition. The panels display findings for four age groups: 35 years (range 30-40 years); 50 years (range 45-55 years); 60 years (range 55-65 years); 80 years (range 75-85 years), based on different LTL attrition rates (15-45 bp/year). For period mortality, the proportion (in %) of individuals reaching an LTL of 5 kb before their life expectancy is based on the aggregate mortality data for a given country and sex at the time of blood collection.

Figure 3

Predicted proportion of the composite study population of males and females reaching the telomere brink (TB; 5 kb) based on period life table mortality (period), life expectancy of 100 years (LE-100), LTL ranking and LTL attrition. The panels display findings for four age groups: 35 years (range 30-40 years); 50 years (range 45-55 years); 60 years (range 55-65 years); 80 years (range 75-85 years), based on different LTL attrition rates (15-45 bp/year).

Figure 4

Predicted proportion of the composite study population reaching the telomere brink (TB; 5 kb) based on period life table mortality (period), life expectancy of 100 years (LE-100), LTL ranking and LTL attrition. Individuals were ranked by quintiles, where the shortest (1st) LTL quintile is 0-19% and the longest (5th) LTL quintile is 80-99%. The panels display findings for four age groups: 35 years (range 30-40 years); 50 years (range 45-55 years); 60 years (range 55-65 years); 80 years (range 75-85 years), based on different LTL attrition rates (15-45 bp/year).