%0 Journal Article %J Aging (Albany NY) %D 2017 %T Telomeres and the natural lifespan limit in humans. %A Steenstrup, Troels %A Kark, Jeremy D %A Verhulst, Simon %A Thinggaard, Mikael %A Hjelmborg, Jacob V B %A DalgÄrd, Christine %A Kyvik, Kirsten Ohm %A Christiansen, Lene %A Mangino, Massimo %A Spector, Timothy D %A Petersen, Inge %A Kimura, Masayuki %A Benetos, Athanase %A Labat, Carlos %A Sinnreich, Ronit %A Hwang, Shih-Jen %A Levy, Daniel %A Hunt, Steven C %A Fitzpatrick, Annette L %A Chen, Wei %A Berenson, Gerald S %A Barbieri, Michelangela %A Paolisso, Giuseppe %A Gadalla, Shahinaz M %A Savage, Sharon A %A Christensen, Kaare %A Yashin, Anatoliy I %A Arbeev, Konstantin G %A Aviv, Abraham %X

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.

%B Aging (Albany NY) %V 9 %P 1130-1142 %8 2017 Apr %G eng %N 4 %R 10.18632/aging.101216 %0 Journal Article %J JAMA Netw Open %D 2020 %T Association of Leukocyte Telomere Length With Mortality Among Adult Participants in 3 Longitudinal Studies. %A Arbeev, Konstantin G %A Verhulst, Simon %A Steenstrup, Troels %A Kark, Jeremy D %A Bagley, Olivia %A Kooperberg, Charles %A Reiner, Alexander P %A Hwang, Shih-Jen %A Levy, Daniel %A Fitzpatrick, Annette L %A Christensen, Kaare %A Yashin, Anatoliy I %A Aviv, Abraham %X

Importance: Leukocyte telomere length (LTL) is a trait associated with risk of cardiovascular disease and cancer, the 2 major disease categories that largely define longevity in the United States. However, it remains unclear whether LTL is associated with the human life span.

Objective: To examine whether LTL is associated with the life span of contemporary humans.

Design, Setting, and Participants: This cohort study included 3259 adults of European ancestry from the Cardiovascular Health Study (CHS), Framingham Heart Study (FHS), and Women's Health Initiative (WHI). Leukocyte telomere length was measured in 1992 and 1997 in the CHS, from 1995 to 1998 in the FHS, and from 1993 to 1998 in the WHI. Data analysis was conducted from February 2017 to December 2019.

Main Outcomes and Measures: Death and LTL, measured by Southern blots of the terminal restriction fragments, were the main outcomes. Cause of death was adjudicated by end point committees.

Results: The analyzed sample included 3259 participants (2342 [71.9%] women), with a median (range) age of 69.0 (50.0-98.0) years at blood collection. The median (range) follow-up until death was 10.9 (0.2-23.0) years in CHS, 19.7 (3.4-23.0) years in FHS, and 16.6 (0.5-20.0) years in WHI. During follow-up, there were 1525 deaths (482 [31.6%] of cardiovascular disease; 373 [24.5%] of cancer, and 670 [43.9%] of other or unknown causes). Short LTL, expressed in residual LTL, was associated with increased mortality risk. Overall, the hazard ratio for all-cause mortality for a 1-kilobase decrease in LTL was 1.34 (95% CI, 1.21-1.47). This association was stronger for noncancer causes of death (cardiovascular death: hazard ratio, 1.28; 95% CI, 1.08-1.52; cancer: hazard ratio, 1.13; 95% CI, 0.93-1.36; and other causes: hazard ratio, 1.53; 95% CI, 1.32-1.77).

Conclusions and Relevance: The results of this study indicate that LTL is associated with a natural life span limit in contemporary humans.

%B JAMA Netw Open %V 3 %P e200023 %8 2020 Feb 05 %G eng %N 2 %R 10.1001/jamanetworkopen.2020.0023