When we are young, our bones heal quickly. Unfortunately, the hand of time diminishes this capacity and we develop conditions affecting our bones and connective tissues. The development of these age-related conditions not only painfully decrease the quality of life, they shorten it.
Fortunately, the powerful intervention of gene therapy is offering us an opportunity to turn back the hand of time, and to rejuvenate the health of our bones. Here we will focus on the remarkable osteo-effects of telomerase and follistatin.
Telomerase is an enzyme that lengthens the ends of our telomeres. Telomere shortening is a significant factor in aging, and a major component of many age-related diseases. For this reason, telomere lengths are known as an effective biomarker for a plethora of age-related diseases and a better means than chronological age of assessing the aging process in humans. (Fossel, 2012)
Telomerase gene therapy has a beneficial effect on a multitude of somatic components and processes. Our bones are not excluded from the list that telomerase positively impacts.
A 2020 review of the current literature revealed that a number of studies suggest that the age-related dysfunction of telomeres negatively affects bone-forming osteoblasts, a process that encourages bone loss and osteoporosis. (Wong, 2020) With this in mind, along with the role telomerase plays in lengthening telomeres, we should turn to what has resulted from research on the effects of telomerase induction on bones.
Telomerase extends the lifespan and bone-forming ability of BMSSCs, a critical type of skeletal stem cells. (Shi, 2002) This suggests telomerase therapy could be used for bone regeneration and repair. Telomerase also facilitates calcium accumulation in BMSSCs and altogether enhances osteogenic differentiation of BMSSCs. (Gronthos, 2003)
As a potential treatment for common age-related bone diseases like osteoporosis, telomerase shows great promise but some studies show its positive reach may extend even farther — into the realm of rare diseases. A study demonstrated that telomerase gene therapy improved survival, telomere length, and blood counts in mice with bone marrow aplasia. (Bär, 2016)
Despite its versatility as a promising treatment for a slew of conditions, there is another powerful gene therapy that extends its reach to our bones. Follistatin, best known for increasing muscle through myostatin inhibition, has several known routes by which it helps.
Research has shown that follistatin has the capacity to combat osteopenia, the diminution of bone density. This is accomplished by blocking GDF-11, a protein that increases with age leading to not only bone loss but reduction in muscle mass. (Egerman, 2015)
Follistatin also has remarkable features as a unique compound acting as an inhibitor of the activin receptor signaling pathway. Indeed, follistatin irreversibly binds to activin A, a protein reported to inhibit bone formation. (Fahmy-Garcia, 2019)
Other compounds that have this property, like follistatin, can increase muscle and bone mass. They are being studied as means of addressing bone and muscle loss. However, follistatin stands out among them because it has no observed effects upon red blood cell count. (Lodberg, 2019)
In a 2019 study, follistatin was investigated for its effects upon key processes in bone repair. The researchers looked for cell recruitment, osteogenesis and vascularization, as well as its usefulness in bone tissue engineering. The findings were very promising, as follistatin was observed to increase committed osteoblast mineralization. The researchers concluded that follistatin enhances the processes needed for bone repair. (Fahmy-Garcia, 2019)
Altogether these therapies grant us the tool to combat the otherwise inexorable process of bone deterioration and the frailty that comes with it. Integrated Health Systems provides these dynamic therapies to confer not only longevity but a better quality of life, a life where increased chronological age does not spell certain debility and disease.
References and Suggested Reading
Fossel M. Use of telomere length as a biomarker for aging and age-related disease. Curr Transl Geriatr Exp Gerontol Rep. 2012;1(2):121–7. https://doi.org/10.1007/s13670-012-0013-6.
Wong, Sok Kuan et al. “Can telomere length predict bone health? A review of current evidence.” Bosnian journal of basic medical sciences vol. 20,4 423-429. 2 Nov. 2020, doi:10.17305/bjbms.2020.4664
Shi S, Gronthos S, Chen S, Reddi A, Counter CM, Robey PG, Wang CY. Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression. Nat Biotechnol. 2002 Jun;20(6):587-91. doi: 10.1038/nbt0602-587. PMID: 12042862.
Gronthos S, Chen S, Wang CY, Robey PG, Shi S. Telomerase accelerates osteogenesis of bone marrow stromal stem cells by upregulation of CBFA1, osterix, and osteocalcin. J Bone Miner Res. 2003 Apr;18(4):716-22. doi: 10.1359/jbmr.2003.18.4.716. PMID: 12674332.
Bär C, Povedano JM, Serrano R, Benitez-Buelga C, Popkes M, Formentini I, Bobadilla M, Bosch F, Blasco MA. Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia. Blood. 2016 Apr 7;127(14):1770-9. doi: 10.1182/blood-2015-08-667485. Epub 2016 Feb 22. PMID: 26903545.
Egerman MA, Cadena SM, Gilbert JA, Meyer A, Nelson HN, Swalley SE, Mallozzi C, Jacobi C, Jennings LL, Clay I, Laurent G, Ma S, Brachat S, Lach-Trifilieff E, Shavlakadze T, Trendelenburg AU, Brack AS, Glass DJ. GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration. Cell Metab. 2015 Jul 7;22(1):164-74. doi: 10.1016/j.cmet.2015.05.010. Epub 2015 May 19. PMID: 26001423; PMCID: PMC4497834.
Fahmy-Garcia, Shorouk et al. “Follistatin Effects in Migration, Vascularization, and Osteogenesis in vitro and Bone Repair in vivo.” Frontiers in bioengineering and biotechnology vol. 7 38. 1 Mar. 2019, doi:10.3389/fbioe.2019.00038
Lodberg A, van der Eerden BCJ, Boers-Sijmons B, Thomsen JS, Brüel A, van Leeuwen JPTM, Eijken M. A follistatin-based molecule increases muscle and bone mass without affecting the red blood cell count in mice. FASEB J. 2019 May;33(5):6001-6010. doi: 10.1096/fj.201801969RR. Epub 2019 Feb 13. PMID: 30759349.
