Short Telomeres Are Heritable and Promote Premature Aging in Mice

Telomeres are DNA buffers located at the end chromosomes that protect their integrity. Every time a cell replicates its DNA a small portion of each telomere is lost. Telomerase is an enzyme that repairs this loss to maintain telomeres; however, its activity decreases with age. The shortening of telomeres leads to the arrest of cellular replication and is postulated to contribute to the natural process of aging. Not surprisingly, telomeres are a hot topic in the anti-aging field of research. A new study in The American Journal of Human Geneticsassessed the role of short telomeres as a heritable trait in premature aging.

The authors generated mice derived from heterozygous telomerase mutants, through successive breeding, that had shortened telomeres and wild type telomerase. In other words, mice with short telomeres and an otherwise normal, or wild type, genome were developed using a successive breeding strategy. Comparisons can be made between the telomere shortened mice and mice with long telomeres for signs of aging.

Telomere length was measured using fluorescent in situ hybridization (FISH) to verify that their breeding strategy produced wild type mice with short telomeres. The shortening of telomeres in wild type mice suggests that short telomeres are heritable, as the wild type short telomere mice are born with normal telomerase. Interestingly, mice with shortened telomeres had lowered bone marrow and spleen cellularity, suggesting defective hematopoeisis. Mice with shortened telomeres also had low B-cell and T-cell function, along with a reduced response to antigen challenge, suggesting the presence of a compromised immune system.

The data presented suggests that short telomeres are a heritable trait that may carry significant consequences for the individual inheriting them. The authors demonstrated that breeding the wild type mice with short telomeres together could eventually rescue telomere length. This suggests that although telomere length is heritable, length can be rescued over successive generations in the presence of normal telomerase. Meaning, normal telomerase function cannot rescue inherited short telomeres after the first generation, but can over numerous generations. Using this logic, genetic disorders that affect telomerase and lead to short telomeres, such as dyskeratosis congenital, may be partly inherited even if progeny from these patients have wild type telomerase activity.

References:

Armanios, M. et, al. The American Journal of Human Genetics 85, 823-832, December 11, 2009.