One of my favorite new stories in the biology of aging is the body of work demonstrating an unexpected (to my mind, anyway) relationship between telomere length and various “organism-scale” phenomena, e.g., psychological stress and cardiovascular disease (CVD).

Two recent reviews extend the discussion. Kajstura et al. focus directly on cellular senescence, which can be induced both by telomeric shortening and genotoxic damage, in cardiac progenitor cells. Does senescence play a role in cardiovascular aging and the age-related onset of CVD?

… Rapidly emerging evidence indicates that new myocytes can be formed through the activation and differentiation of resident cardiac progenitor cells. The critical issue is the identification of mechanisms that define the aging of cardiac progenitor cells and, ultimately, their inability to replace dying myocytes. The most reliable marker of cellular senescence is the modification of the telomere–telomerase axis, together with the expression of the cell cycle inhibitors p16INK4a and p53. … In this regard, one of the most relevant processes is represented by repeated oxidative stress that may evolve into the activation of the cell death program or result in the development of a senescent phenotype. Thus, the modulation of telomerase activity and the control of telomeric length, together with the attenuation of the formation of reactive oxygen species, may represent important therapeutic tools in regenerative medicine and in prevention of aging and diabetic cardiomyopathies.

Fuster and Andrés summarize the evidence linking telomere dysfunction to CVD risk factors and CVD itself. (emphasis is mine)

… we discuss experimental and human studies that have linked telomeres and associated proteins to several factors which influence cardiovascular risk (eg, estrogens, oxidative stress, hypertension, diabetes, and psychological stress), as well as to neovascularization and the pathogenesis of atherosclerosis and heart disease. Two chief questions that remain unanswered are whether telomere shortening is cause or consequence of cardiovascular disease, and whether therapies targeting the telomere may find application in treating these disorders (eg, cell “telomerization” to engineer blood vessels of clinical value for bypass surgery, and to facilitate cell-based myocardial regeneration strategies). Given that most research to date has focused on the role of telomerase, it is also of up most importance to investigate whether alterations in additional telomere-associated proteins may contribute to the pathogenesis of cardiovascular disease.

The emphasized passage raises a critical question: Since the telomere-telomerase axis can be altered both by aging and by stress, it’s important to know whether telomere shortening is driving or merely signposting age-related change. Indeed, if therapeutics based on telomeres are to be developed, this knowledge is essential.