The Nobel Prize in Physiology or Medicine 2009: "how chromosomes are protected by telomeres and the enzyme telomerase"
The Nobel Assembly at Karolinska Institutet awarded jointly to Elizabeth H. Blackburn (Professor of biology and physiology at the University of California, San Francisco), Carol W. Greider (Professor in the department of molecular biology and genetics at Johns Hopkins University School of Medicine in Baltimore), and Jack W. Szostakfor (He has been at Harvard Medical School since 1979 and is currently professor of genetics at Massachusetts General Hospital in Boston.) the discovery.
2009's Nobel Prize in Physiology or Medicine was awarded to three scientists who solved a major problem in biology: how the chromosomes can be copied in a complete way during cell divisions and how they are protected against degradation. The Nobel Laureates have shown that the solution is to be found in the ends of the chromosomes – the telomeres – and in an enzyme that forms them – telomerase.
The long, thread-like DNA molecules that carry our genes are packed into chromosomes, the telomeres being the caps on their ends. Elizabeth Blackburn and Jack Szostak discovered that a unique DNA sequence in the telomeres protects the chromosomes from degradation. Carol Greider and Elizabeth Blackburn identified telomerase, the enzyme that makes telomere DNA. These discoveries explained how the ends of the chromosomes are protected by the telomeres and that they are built by telomerase.
If the telomeres are shortened, cells age. Conversely, if telomerase activity is high, telomere length is maintained, and cellular senescence is delayed. This is the case in cancer cells, which can be considered to have eternal life. Certain inherited diseases, in contrast, are characterized by a defective telomerase, resulting in damaged cells. The award of the Nobel Prize recognizes the discovery of a fundamental mechanism in the cell, a discovery that has stimulated the development of new therapeutic strategies. Simply incredible telomere award-winning work.
Multivitamin use and telomere length in women *
Background: Telomere length may be a marker of biological aging. Background: Telomere length may be a marker of biological aging trients, which may affect telomere length by modulating oxidative stress and chronic inﬂammation.
Objective: The objective was to examine whether multivitamin use is associated with longer telomeres in women.
Design: We performed a cross-sectional analysis of data from 586 early participants (age 35–74 y) in the Sister Study. Multivitamin use and nutrient intakes were assessed with a 146-item food-frequency questionnaire, and relative telomere length of leukocyte DNA was measured by quantitative polymerase chain reaction.
Results: After age and other potential confounders were adjusted for, multivitamin use was associated with longer telomeres. Compared with nonusers, the relative telomere length of leukocyte DNA was on average 5.1% longer among daily multivitamin users (P for trend ¼ 0.002). In the analysis of micronutrients, higher intakes of vitamins C and E from foods were each associated with longer telomeres, even after adjustment for multivitamin use. Furthermore intakes of both nutrients were associated with telomere length among women who did not take multivitamins.
Conclusion: This study provides the ﬁrst epidemiologic evidence that multivitamin use is associated with longer telomere length among women. Am J Clin Nutr 2009;89:1857–63. Incredible information on telomere length.
Telomerase deficiency promotes oxadative stress by reducing catalse activity **
"...the first experimental evidence of a direct relationship between telomerase deficiency and increased oxidative stress..."
Aging is an unavoidable process for all multicellular species, and is characterized by a progressive decline in efficiency of physiological functions. It is generally thought that aging is the result of a combination of environment and genetic factors.
Among the environmental factors, the free radical theory of aging proposed by Harman is the most widely accepted . This author postulated that aging could be attributed to the deleterious effect of reactive oxygen species (ROS) on cell components. Different experimental approaches have been used to demonstrate this hypothesis. In general, oxidative damage increases exponentially with age , ROS generation rates rise, and antioxidant defenses can diminish in aged organism [3,4].
While in aerobic organisms, physiological ROS concentrations are involved in cell signaling pathways and in defense against pathogens, an imbalance due to elevated ROS concentrations could contribute to the pathogenesis of diseases such as cancer, hypertension, diabetes, atherosclerosis, or premature aging .
Higher serum vitamin D concentrations are associated with longer leukocyle telomere length in women ***
"...vitamin D may play a role in the modulation of LTL, which is related in aging and age-related disease"
Mounting evidence suggests that, in addition to its well-described roles in skin, bone, and muscle physiology (2), the hormone vitamin D acts as an inhibitor of the inflammatory response through several pathways (1). Decreased vitamin D concentrations have been associated with an increased risk of developing autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and type 1 diabetes (3-6).
Vitamin D administration has been shown to prevent the initiation and to attenuate the severity of immune-mediated diseases, including type 1 diabetes (7-8) and an animal model for multiple sclerosis (9). In addition, a recent open-label trial showed that vitamin D decreased rheumatoid arthritis disease activity (10)..
Effect of Resveratrol on Proliferation and Telomerase Activity Activity of Human Colon Cancer Cells Vitro *^
"...telomerase could be a novel and selective target for antitumor drug design.."
A number of studies performed in our laboratory and elsewhere, showed that resveratrol is able to prevent carcinogenesis and to impair tumor growth and progression. In order to provide additional information on the pleiotropic effects of resveratrol on malignant cells, the present study was performed to test the in vitro influence of the compound on the growth and TLMA of HT-29 and WiDr human colon cancer cell lines. The results confirmed that resveratrol has a direct, dose dependent, inhibitory effect on cell proliferation in both lines.
In addition, for the first time, relatively high concentrations of this compound were found to be able to substantially down-regulate telomerase activity. These preliminary results further support the potential role of resveratrol in chemoprevention/chemotherapy of human colon tumor cells and provide the rational basis for novel strategies in cancer control.
Intermountain study finds length of DNA strands can predict life expectancy *^^
"...research shows that if we statistically adjust for age, patient with longer telomeres live longer..."
Can the length of strands of DNA in patients with heart disease predict their life expectancy? Researchers from Intermountain Heart Institute at Intermountain Medical Center in Salt Lake City, who studied the DNA of more than 3,500 patients with heart disease, say yes it can.
In the new study, presented Saturday, March 9, at the American College of Cardiology’s Annual Scientific Session in San Francisco, the researchers were able to predict survival rates among patients with heart disease based on the length of strands of DNA found on the ends of chromosomes known as telomeres – the longer the patient’s telomeres, the greater the chance of living a longer life.
Telomeres, lifestyle, cancer, and aging *^^^
Purpose of review—There has been growing evidence that lifestyle factors may affect the health and lifespan of an individual by affecting telomere length. The purpose of this review was to highlight the importance of telomeres in human health and aging and to summarize possible lifestyle factors that may affect health and longevity by altering the rate of telomere shortening.
Recent findings—Recent studies indicate that telomere length, which can be affected by various lifestyle factors, can affect the pace of aging and onset of age-associated diseases.
Summary—Telomere length shortens with age. Progressive shortening of telomeres leads to senescence, apoptosis, or oncogenic transformation of somatic cells, affecting the health and lifespan of an individual. Shorter telomeres have been associated with increased incidence of diseases and poor survival. The rate of telomere shortening can be either increased or decreased by specific lifestyle factors. Better choice of diet and activities has great potential to reduce the rate of telomere shortening or at least prevent excessive telomere attrition, leading to delayed onset of age-associated diseases and increased lifespan. This review highlights the role of telomeres in aging and describes the lifestyle factors which may affect telomeres, human health, and aging.
Potential involvement of oxidative stress in cartilage senescence and development of osteoarthritis- oxidative stress induces chondrocyte telomere instability and downregulation of chondrocyte function*^^^^
The findings of the present study suggest that cumulative The findings of the present study suggest that cumulative ity in articular cartilage, resulting in chondrocyte telomere shortening, regardless of cell proliferation. Oxidative stress shortening, regardless of cell proliferation. Oxidative stress cence in chondrocytes and resultant cartilage ageing.
This study provides insight into the involvement of oxidative stress in the pathogenesis of OA from the viewpoint of oxistress in the pathogenesis of OA from the viewpoint of oxiomere erosion, and chondrocyte senescence. Our findings omere erosion, and chondrocyte senescence. Our findings omere erosion, and chondrocyte senescence. Our findings function of chondrocytes in vitro and in vivo, suggesting a role for oxidative stress in the development of OA. Also, our results suggest that antioxidative agents are effective in results suggest that antioxidative agents are effective in lage degeneration. New efforts to prevent the development lage degeneration. New efforts to prevent the development tions aimed at reducing oxidative damage in articular cartilage.
The author(s) declare that they have no competing interests.
* from "The American Journal of Clinical Nutrition;" Qun Xu, Christine G Parks, Lisa A DeRoo, Richard M Cawthon, Dale P Sandler, and Honglei Chen
** from "Free Radical Biology & Medicine;" Gema Perez-Rivero, Maria P. Ruiz-Torres, Maria L Diez-Marques, Manuel Rodriquiez-Puyol (University of Alcala of Henares; Madrid, Spain); Jose M. Lopez-Noroa (University of salamanca; Salamanca, Spain); Maria A. Blasco, Diego Rodriguez-Puyol (University of Alcala; Madrid, Spain); Andres Canola
*** from "The American Journal of Clinical Nutrition;" J. Brent Richards, Ana M. Valdes, Jeffrey P. Gardner, Dimitri Paximadas, Masayuki Kimura, Ayran Nessa, Xiaobin Lu, Gabriela L. Surdulescu, Rami Swaminathan, Tim D. Specotr, Abraham Aviv
*^ from "J. Exp. Clin. Cancer Res., 25, 2, 2006;" M.P. Fuggetta, G. Lanzill, M. Tricarico, A. Cottarel, R. Falchetti, G. Raragnan, E. Bonmassar; Institute of Neurobiology and Molecular Medicine, National Research Council- CNR, Department of Environmental Science, University of Tor Vergata, Rome; Department of Environmental Science, Ca Fescari; University of Venice, Venice- Italy
*^^ from "Intermountain Medical Center Heart Institute at Intermountain Medical Center in Murray, Utah;" John Carlquist, PhD; Stacey Knight, PhD; Benjamin Horne, PhD; Jeffrey Rollo, BS; John Huntinghouse, BS; Brent Muhlestein, MD; Jeffrey Anderson, MD
*^^^ "Harvard (Dana Farber) Cancer Institute, Boston, Massachusetts, USA;" Masood A. Shammas
*^^^^ Kazuo Yudoh, Nguyen van Trieu, Hiroshi Nakamura, Kayo Hongo-Masuko, Tomohiro Kato and Kusuki Nishioka Department of Bioregulation, Institute of Medical Science, St. Marianna University, Kawasaki City, Japan; Corresponding author: Kazuo Yudoh, email@example.com; Received: 13 Nov 2003 Revisions requested: 4 Dec 2003 Revisions received: 25 Nov 2004 Accepted: 10 Dec 2004 Published: 26 Jan 2005; Arthritis Res Ther 2005, 7:R380-R391 (DOI 10.1186/ar1499)http://arthritis-research.com/content/7/2/R380; © 2005 Yudoh et al.; licensee BioMed Central Ltd.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.