Prevent Telomere ShorteningDecember 2016
By Miles Mueller
Like the burning of a fuse, telomeres at the ends of our chromosomes steadily shorten every time a cell replicates itself.1,2
A study from The Lancet evaluating telomere length on a group of individuals age 60 and over found that those with shorter telomeres had a 3.18-fold higher mortality rate from heart disease and an 8.54-fold higher mortality rate from infectious disease.3
Telomeres, which are made up of repeating units of DNA sequences, hold the key to biological aging.4 Once telomeres reach a critically short length, further cellular replications are prevented, leading to aging (senescence) of the cell.1,2,5
These senescent cells eventually accumulate or die. Senescent cells no longer contribute to active tissue maintenance.1,2 In fact, telomere length has become useful as a biomarker of cellular aging.4-7
Studies show plenty of triggers that accelerate telomere shortening, including oxidative stresses, inflammation, and obesity.1,8 Shortened telomeres are found in people with age-related disorders such as cardiovascular disease, diabetes, neurodegeneration, and osteoporosis.9,10 Not surprisingly then, the search is on for ways to preserve telomere length in normal cells, with the aim of sustaining cellular youth and healthy functioning.
Cells naturally contain an enzyme called telomerase, which adds new DNA to the ends of telomeres, helping to keep them long enough to support cellular activities.11 In the past few years, scientists have accumulated an impressive array of evidence showing that one way of supporting healthy, long telomeres is to get an adequate intake of vitamins.4,11-14
There is now intriguing evidence demonstrating how supplemental vitamins can preserve telomere length and sustain more youthful cell functions.
B Vitamins Preserve Telomere Length
The B vitamins, including vitamins B6, B12, and folate, are essential factors in the metabolism of the molecules that make up DNA.6 Their importance is therefore critical in supporting normal cellular replication. Low levels of B vitamins are common in aging adults, and are closely associated with risk for developing age-related diseases.5,15
Homocysteine is a molecule associated with increased cardiovascular disease risk and poor blood vessel function. B vitamins are necessary for normal disposal of homocysteine, which accumulates under conditions of B vitamin deficiency. Both elevated homocysteine levels and diminished B vitamin levels are closely associated with premature shortening of telomeres, leading to accelerated cellular aging.5,15,16 Thus, homocysteine-induced telomere shortening may be the central connection between B vitamin deficiency, high homocysteine levels and cardiovascular disease.16
It has long been known that B vitamin supplementation reduces homocysteine levels, and it was recently shown that people whose B vitamin levels are low have shorter telomeres.5,15
Taken together, these findings suggest that keeping B vitamins at adequate levels is an effective means of both lowering toxic homocysteine levels and supporting longer telomeres.
Vitamin D Promotes Telomerase Activity
Long thought to be limited to promoting calcium absorption in the intestines, vitamin D has become known as one of the most versatile of nutrients.10 Vitamin D receptors are found on cells throughout the body, suggesting that still more functions await discovery.17
Recently, a molecular link was found between vitamin D and DNA repair an action required for maintenance of telomere length.18 Higher plasma vitamin D levels have been associated with longer telomeres.19 These findings have triggered other studies of vitamin D and its role in telomere function.
For example, patients undergoing hemodialysis for kidney failure have both decreased telomere length and lower vitamin D levels compared with healthy controls.12 But dialysis patients treated with vitamin D3 were shown to have longer telomeres than untreated patients, potentially explaining the beneficial health effects of supplementation in these individuals.12
In a more generalized study, vitamin D supplementation in a group of overweight Americans, at a dose of 2000 IU/day, increased subjects’ telomerase activity by more than 19%.1 This finding suggests that vitamin D plays an important role in supporting telomere lengthening and as a result has antiaging potential.
Vitamins C and E Preserve Telomere Length
Studies of vitamin C demonstrate that telomere shortening can be reduced by up to 62% on untreated controls in cultures of human blood vessel cells.20 The result was a significant extension of cellular lifespan, and reduction in physical changes associated with cell aging. This in turn was associated with sharp reductions in cellular free radicals.20
Near-identical results have now been shown in cultures of human heart-muscle cells, demonstrating that vitamin C can work to slow cardiovascular aging by preserving telomere length.21
A dramatic demonstration of the value of vitamin C’s role in aging-deceleration was provided by a 2016 study of cellular model of Werner Syndrome, a premature aging disorder.22 After testing numerous compounds for their ability to slow or reverse the rapid aging, scientists identified vitamin C as the most efficient “rescue” for many premature aging characteristics of the cells.22 Treated cells showed longer telomeres, reduced secretion of inflammatory cytokines, and improved integrity of their cellular nuclei, all features of much younger cells. Indeed, in a mouse model of Werner Syndrome, vitamin C rescued aging cells from premature death by altering expression of genes involved in the maintenance of DNA integrity.22
Vitamin E comes in a total of 8 different forms, four each in the tocopherol and tocotrienol categories. Alpha-tocopherol, one of the most-studied forms of vitamin E, dramatically slows age-related telomere shortening, even in the presence of powerful oxidant molecules such as hydrogen peroxide.13,14 This has been proven to result from a tocopherol-induced increase in telomerase that persists even into middle-aged cells.14 Similar results have been shown in cells treated with gamma-tocotrienol, which not only prevented telomere shortening but also enhanced the viability of older cells in culture.23
In a dramatic finding, incubating aging human cells with a tocotrienol-rich formulation reversed the aging-induced structural changes to cells to the point that they resembled younger cells, with less DNA damage and more cells ready for fruitful replication.24 Here again, the effects were attributable to increased telomerase activity.24
Carotenoids Associated with Longer Telomeres
Carotenoids are yellow pigment molecules closely related to Vitamin A. Their molecular structures promote their powerful antioxidant actions, though they also appear to have other effects.
Studies show that older people with higher plasma levels of the carotenoids lutein and zeaxanthin have significantly longer telomeres than those with lower levels.25 In people 20 years and older, a doubling of blood levels of alpha-carotene, beta-carotene, and beta-cryptoxanthin was associated with 2% longer telomeres.7 Those with the highest carotenoid levels had telomeres 5% to 8% longer than those in the lowest category.7
Intake of the carotenoid nutrients is also closely associated with longer telomeres, although this effect may depend to some extent on genetic factors related to carotene metabolism.26
While aging is a many-faceted process, a clear-cut biomarker for aging at the cellular level has been found in measurements of telomere length.
Shortening telomeres accelerate cellular aging, but nutrients that promote telomere repair and sustain telomere length have proven health benefits.
In recent years, we have learned that even common vitamins can have dramatic impact on the lengths of the telomeres in our cells, thereby powerfully decelerating aging at the cell, tissue, organ, and whole organism levels.
B vitamins preserve telomere length in part by lowering homocysteine, which accelerates telomere shortening.
Vitamin D promotes activity of telomerase, the repair enzyme that steadily adds to telomere length.
Vitamins C and E preserve telomere length by reducing the chemical stresses that contribute to telomere shortening. Gamma-tocotrienol in particular may reverse telomere shortening and attendant cellular aging.
Finally, the vegetable carotenoids, such as lutein, contribute to longer telomeres, though mechanisms for these effects remain to be discovered.
Without question, supporting a well-rounded diet with ample basic vitamins has emerged as an invaluable antiaging intervention.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Zhu H, Guo D, Li K, et al. Increased telomerase activity and vitamin D supplementation in overweight African Americans. Int J Obes (Lond). 2012;36(6):805-9.
- Chiappori AA, Kolevska T, Spigel DR, et al. A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small-cell lung cancer. Ann Oncol. 2015;26(2):354-62.
- Cawthon RM, Smith KR, O’Brien E, et al. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet. 2003;361(9355):393-5.
- Xu Q, Parks CG, DeRoo LA, et al. Multivitamin use and telomere length in women. Am J Clin Nutr. 2009;89(6):1857-63.
- Pusceddu I, Herrmann M, Kirsch SH, et al. One-carbon metabolites and telomere length in a prospective and randomized study of B- and/or D-vitamin supplementation. Eur J Nutr. 2016.
- Shin C, Baik I. Leukocyte Telomere Length is Associated With Serum Vitamin B12 and Homocysteine Levels in Older Adults With the Presence of Systemic Inflammation. Clin Nutr Res. 2016;5(1):7-14.
- Min KB, Min JY. Association between leukocyte telomere length and serum carotenoid in US adults. Eur J Nutr. 2016.
- Zhang D, Sun X, Liu J, et al. Homocysteine accelerates senescence of endothelial cells via DNA hypomethylation of human telomerase reverse transcriptase. Arterioscler Thromb Vasc Biol. 2015;35(1):71-8.
- Xiong S, Patrushev N, Forouzandeh F, et al. PGC-1alpha Modulates Telomere Function and DNA Damage in Protecting against Aging-Related Chronic Diseases. Cell Rep. 2015;12(9):1391-9.
- Pusceddu I, Farrell CJ, Di Pierro AM, et al. The role of telomeres and vitamin D in cellular aging and age-related diseases. Clin Chem Lab Med. 2015;53(11):1661-78.
- Harley CB, Liu W, Flom PL, et al. A natural product telomerase activator as part of a health maintenance program: metabolic and cardiovascular response. Rejuvenation Res. 2013;16(5):386-95.
- Borras M, Panizo S, Sarro F, et al. Assessment of the potential role of active vitamin D treatment in telomere length: a case-control study in hemodialysis patients. Clin Ther. 2012;34(4):849-56.
- Makpol S, Zainuddin A, Rahim NA, et al. Alpha-tocopherol modulates hydrogen peroxide-induced DNA damage and telomere shortening of human skin fibroblasts derived from differently aged individuals. Planta Med. 2010;76(9):869-75.
- Tanaka Y, Moritoh Y, Miwa N. Age-dependent telomere-shortening is repressed by phosphorylated alpha-tocopherol together with cellular longevity and intracellular oxidative-stress reduction in human brain microvascular endotheliocytes. J Cell Biochem. 2007;102(3):689-703.
- Pusceddu I, Herrmann M, Kirsch SH, et al. Prospective study of telomere length and LINE-1 methylation in peripheral blood cells: the role of B vitamins supplementation. Eur J Nutr. 2016;55(5):1863-73.
- Rane G, Koh WP, Kanchi MM, et al. Association Between Leukocyte Telomere Length and Plasma Homocysteine in a Singapore Chinese Population. Rejuvenation Res. 2015;18(3):203-10.
- Bikle DD. Vitamin D: an ancient hormone. Exp Dermatol. 2011;20(1):7-13.
- Gonzalez-Suarez I, Redwood AB, Grotsky DA, et al. A new pathway that regulates 53BP1 stability implicates cathepsin L and vitamin D in DNA repair. Embo j. 2011;30(16):3383-96.
- Liu JJ, Prescott J, Giovannucci E, et al. Plasma vitamin D biomarkers and leukocyte telomere length. Am J Epidemiol. 2013;177(12):1411-7.
- Furumoto K, Inoue E, Nagao N, et al. Age-dependent telomere shortening is slowed down by enrichment of intracellular vitamin C via suppression of oxidative stress. Life Sci. 1998;63(11):935-48.
- Kim YY, Ku SY, Huh Y, et al. Anti-aging effects of vitamin C on human pluripotent stem cell-derived cardiomyocytes. Age (Dordr). 2013;35(5):1545-57.
- Li Y, Zhang W, Chang L, et al. Vitamin C alleviates aging defects in a stem cell model for Werner syndrome. Protein Cell. 2016;7(7):478-88.
- Makpol S, Abidin AZ, Sairin K, et al. gamma-Tocotrienol prevents oxidative stress-induced telomere shortening in human fibroblasts derived from different aged individuals. Oxid Med Cell Longev. 2010;3(1):35-43.
- Makpol S, Durani LW, Chua KH, et al. Tocotrienol-rich fraction prevents cell cycle arrest and elongates telomere length in senescent human diploid fibroblasts. J Biomed Biotechnol. 2011;2011:506171.
- Sen A, Marsche G, Freudenberger P, et al. Association between higher plasma lutein, zeaxanthin, and vitamin C concentrations and longer telomere length: results of the Austrian Stroke Prevention Study. J Am Geriatr Soc. 2014;62(2):222-9.
- Yabuta S, Masaki M, Shidoji Y. Associations of Buccal Cell Telomere Length with Daily Intake of beta-Carotene or alpha-Tocopherol Are Dependent on Carotenoid Metabolism-related Gene Polymorphisms in Healthy Japanese Adults. J Nutr Health Aging. 2016;20(3):267-74.
- Kiecolt-Glaser JK, Epel ES, Belury MA, et al. Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial. Brain Behav Immun. 2013;28:16-24.