Journal
AGING CELL
Volume 21, Issue 5, Pages -Publisher
WILEY
DOI: 10.1111/acel.13614
Keywords
cardiovascular disease; DKC1; dyskerin; immune disorders; lifespan; sex differences; telomerase; telomere length; X chromosome inactivation
Categories
Funding
- Canadian Institutes of Health Research [PJT--159787]
- Canada Foundation for Innovation [40044]
- Terry Fox Research Institute [1074]
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Telomerase levels in most human cells are insufficient to prevent loss of telomeric DNA with each replication cycle. The resulting Hayflick limit may have allowed lifespan to increase by suppressing early tumor development but compromising cellular responses later in life. Average telomere length in leukocytes varies considerably between individuals, with females having longer telomeres than males. This difference in telomere length already exists at birth and corresponds to reported differences in average life expectancy between the sexes. The hypothesis that embryonic telomerase levels contribute to the sex differences in telomere length and lifespan requires further investigation.
Telomerase levels in most human cells are insufficient to prevent loss of telomeric DNA with each replication cycle. The resulting Hayflick limit may have allowed lifespan to increase by suppressing the development of tumors early in life be it at the expense of compromised cellular responses late in life. At any given age, the average telomere length in leukocytes shows considerably variation between individuals with females having, on average, longer telomeres than males. Sex differences in average telomere length are already present at birth and correspond to reported differences in the average life expectancy between the sexes. Levels of telomerase RNA and dyskerin, encoded by DKC1, are known to limit telomerase activity in embryonic stem cells. X-linked DKC1 is expressed from both alleles in female embryo cells and higher levels of dyskerin and telomerase could elongate telomeres prior to embryo implantation. The hypothesis that embryonic telomerase levels set the stage for the sex differences in telomere length and lifespan deserves further study.
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