• Open Access

Short telomeres: cause or consequence of aging?


  • Peter J. Hornsby

    1. Department of Physiology and Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA
    Search for more papers by this author

Peter J. Hornsby, Department of Physiology and Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA. Tel.: 210 562 5080; fax: 281 582 3538; e-mail: hornsby@uthscsa.edu


Questions about mechanisms, about the direction of causality, and about cellular heterogeneity complicate interpretation of claims associating short telomeres with adverse health outcomes.

The findings of Cherkas et al. raise a key question: are short telomeres, as evidenced by short telomeres in white blood cells, a cause of biological aging or a harmless by-product of age-related processes?

The relatively short length of human telomeres (compared to those of many other mammals) appears to form part of an anticancer mechanism. Cancer cells that cannot call upon telomerase to maintain their telomeres over multiple rounds of division have a limited growth potential, and such a tumor can only reach a size, perhaps 1–2 g, big enough to kill a mouse but small in the context of the human body (Sun et al., 2005). Some have argued that short telomeres lead, in old age, to tissue malfunctions, the price we as a species pay for anticancer protection at younger ages (Campisi, 2003). But is there any direct evidence that short telomeres in tissues do cause functional impairments? Mice engineered to have shorter telomeres exhibit abnormalities of gut, skin, and blood cells (Blasco, 2005), demonstrating that sufficiently short telomeres can have an adverse impact on tissue function. Experiments in mice, however, cannot show whether telomeres ever reach a length that impairs proliferation in any tissue in humans during a normal lifespan. Telomere shortening certainly occurs in aging humans, in cell types including smooth muscle cells, endothelial cells, lens epithelial cells, muscle satellite cells, T cells and adrenocortical cells, but there is in fact little evidence that impaired proliferation contributes to commonly observed changes in older individuals such as anemia and impaired wound healing (Hornsby, 2001). Studies of human bone marrow-transplant recipients provide some insights here: the hematopoietic system of these patients can exhibit dramatic telomere shortening (Wynn et al., 1998), perhaps contributing to the immune dysfunction often seen in this clinical setting (Lewis et al., 2004).

In view of the available information, how do we interpret epidemiological studies that relate telomere length (in white blood cells) to various measures of survival, health or, in this case, socio-economic status? Cherkas et al. conclude that ‘in and of itself, socio-economic status appears to have an impact on white blood cell telomere dynamics’. A previous study on mothers of chronically ill children concluded that ‘psychological stress is associated with indicators of accelerated cellular aging [including] telomere length’ (Epel et al., 2004). Both of those studies suggest an influence of perceived psychological status on telomere length. An issue that immediately arises here is the multiple uses of the word ‘stress’ in biology, medicine, and psychology. Psychological stress does not necessarily cause stress at the cellular/molecular level. One plausible link is the endocrine system (Cohen et al., 2006). Possibly, differences in telomere length in individuals of differing socio-economic status result from the actions of hormones such as glucocorticoids on cell death and cell proliferation in the hematopoietic system.

We are still left with the central question of whether the shorter telomeres in individuals of lower socio-economic status have an adverse effect on health or mortality. Might short telomeres be only an age-associated but benign or inconsequential marker, like graying of the hair or senile lentigenes of the skin? These age-related changes do result from profound alterations in melanocytes, including melanocyte stem cells (Nishimura et al., 2005), but do not cause age-related morbidity or mortality. There are at three least major questions that need to be answered. First, we need to know what telomere length in human tissues is associated with functional impairment. Second, because of the great heterogeneity in telomere lengths between cells and between different telomeres within cells, we need to know if there could be impairment of subsets of cells, even if there is no measurable deficit in the cell population as a whole. Third, we do not know if telomere length in white blood cells correlates with telomere length in other tissues. Gaining access to appropriate tissue samples to test this is problematic. This is a chicken-and-egg type of question: What is the critical cell population that might be most important to study in terms of telomere shortening? However, if we knew which cells to examine then it is likely that we would already have the answer to the question of the significance of telomere shortening in human aging.