There is a contingent of researchers who see increased levels of telomerase as a viable therapy to slow aging, and shortened telomeres as a contributing cause of aging. Below find linked an open access paper written from that perspective.
It is certainly the case that genetic engineering of mice to produce additional telomerase results in a modest extension of life, though not as much as initially reported. It seems to generally boost regenerative activity, which results in similar outcomes to stem cell therapies. The primary mechanism associated with telomerase is the lengthening of telomeres, the repeated DNA sequences at the end of chromosomes that act as a counter of cell divisions - a little is lost each time a cell divides and replicates its DNA. While some researchers see shortened telomeres as a cause of aging, it seems pretty clear to me, and others, that average telomere length as presently measured is a reflection of processes of aging, not a cause. There has in the past been some discussion of other ways in which telomerase might be acting on life span, such as by affecting the pace of mitochondrial damage, for example.
In this review, we will discuss the role of telomeres in the origin of age-associated diseases and organismal longevity, as well as the potential use of telomerase as a therapeutic target to delay aging and to prevent and treat age-related diseases. Aging is a multifactorial process that results in a progressive functional decline at cellular, tissue, and organismal levels. During recent years, a number of molecular pathways have been identified as main molecular causes of aging, including telomere attrition, cellular senescence, genomic instability, stem cell exhaustion, mitochondrial dysfunction, and epigenetic alterations, among others. Interestingly, telomere attrition is considered a primary cause of aging, as it can trigger all the above-mentioned hallmarks of aging, although the degree to which it is a principal cause of aging is under active investigation. Critical telomere shortening elicits the induction of cellular senescence or the permanent inability of cells to further divide, which in turn has been proposed to be at the origin of different disease states. In addition, telomere attrition in the stem cell compartments results in the exhaustion of their tissue- and self-renewal capacity, thus also leading to age-related pathologies.
A substantial number of companies are now aiming to harness the knowledge that has been generated, unveiling the molecular mechanisms of aging in order to develop a new class of drugs to prevent and treat the major age-related diseases. In this regard, telomerase overexpression studies in mice have been proof of principle that just modifying a single hallmark of aging, i.e. telomere shortening, this was sufficient to delay not one but many different age-associated pathologies in mice, including cognitive decline. Indeed, the use of telomerase activation in delaying aging-associated conditions has spurred the interest of commercial enterprises.
It is likely that the first clinical use of a telomerase reverse transcriptase (TERT)-based therapy, such as the TERT gene therapy approach developed by us, will be for the treatment of the human telomere syndromes, including aplastic anemia and pulmonary fibrosis. However, this requires the development of appropriate preclinical models and the subsequent clinical trials in humans. In this regard, we have recently generated two mouse models which recapitulate the clinical features of aplastic anemia and pulmonary fibrosis. The disease in both models is provoked by short and dysfunctional telomeres and thus these models provide a platform for further testing of TERT-based treatment strategies for the telomere syndromes.
Given that physiological aging is provoked, at least in part, by telomere shortening, a TERT gene therapy may be used not only for the prevention and treatment of telomere syndromes but also for the treatment of multiple age-related diseases. In this regard, short telomeres have been extensively associated with a higher risk for cardiovascular disease. In support of a potential use of TERT activation in the treatment of age-related diseases, we demonstrated that TERT gene therapy can efficiently rescue mouse survival and heart scarring in a preclinical mouse model for heart failure upon induction of acute myocardial infarction. Collectively, experiments in cell and animal models provide proof of concept for the feasibility of telomerase activation approaches to counteract telomere shortening and its consequences. In particular, the successful use of telomerase gene therapy in animal models of aging and short telomere-related diseases paves the way for the development of therapeutic telomerase treatments in human aging and associated disease.