Telomerase reverse transcriptase synergizes with calorie restriction to increase health span and extend mouse longevity
Caloric restriction (CR), a reduction of food intake while avoiding malnutrition, can delay the onset of cancer and age-related diseases in several species, including mice. In addition, depending of the genetic background, CR can also increase or decrease mouse longevity. This has highlighted the im...
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| description | Caloric restriction (CR), a reduction of food intake while avoiding malnutrition, can delay the onset of cancer and age-related diseases in several species, including mice. In addition, depending of the genetic background, CR can also increase or decrease mouse longevity. This has highlighted the importance of identifying the molecular pathways that interplay with CR in modulating longevity. Significant lifespan extension in mice has been recently achieved through over-expression of the catalytic subunit of mouse telomerase (mTERT) in a cancer protective background. Given the CR cancer-protective effects in rodents, we set to address here whether CR impacts on telomere length and synergizes with mTERT to extend mouse longevity. CR significantly decreased tumor incidence in TERT transgenic (TgTERT) mice and extended their lifespan compared to wild-type (WT) controls under the same diet, indicating a synergy between TgTERT and CR in increasing mouse longevity. In addition, longitudinal telomere length measurements in peripheral blood leukocytes from individual mice showed that CR resulted in maintenance and/or elongation telomeres in a percentage of WT mice, a situation that mimics telomere dynamics in TgTERT cohorts. These results demonstrate that CR attenuates telomere erosion associated to aging and that synergizes with TERT over-expression in increasing "health span" and extending mouse longevity. |
| doi_str_mv | 10.1371/journal.pone.0053760 |
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In addition, depending of the genetic background, CR can also increase or decrease mouse longevity. This has highlighted the importance of identifying the molecular pathways that interplay with CR in modulating longevity. Significant lifespan extension in mice has been recently achieved through over-expression of the catalytic subunit of mouse telomerase (mTERT) in a cancer protective background. Given the CR cancer-protective effects in rodents, we set to address here whether CR impacts on telomere length and synergizes with mTERT to extend mouse longevity. CR significantly decreased tumor incidence in TERT transgenic (TgTERT) mice and extended their lifespan compared to wild-type (WT) controls under the same diet, indicating a synergy between TgTERT and CR in increasing mouse longevity. In addition, longitudinal telomere length measurements in peripheral blood leukocytes from individual mice showed that CR resulted in maintenance and/or elongation telomeres in a percentage of WT mice, a situation that mimics telomere dynamics in TgTERT cohorts. These results demonstrate that CR attenuates telomere erosion associated to aging and that synergizes with TERT over-expression in increasing "health span" and extending mouse longevity.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0053760</identifier><identifier>PMID: 23349740</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Aging ; Aging - genetics ; Aging - physiology ; Animals ; Apoptosis ; Biology ; Biomarkers - metabolism ; Body Weight - genetics ; Body Weight - physiology ; Caloric Restriction ; Cancer ; Catalysis ; Cell division ; Chromosome Aberrations ; Chromosomes ; Deoxyribonucleic acid ; Diabetes ; Dietary restrictions ; Disease ; DNA ; Elongation ; Food intake ; Genetic engineering ; Health ; Humans ; Leukocytes ; Life span ; Longevity ; Longevity - genetics ; Longevity - physiology ; Longitudinal Studies ; Male ; Malnutrition ; Mammals ; Medical research ; Medicine ; Metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nutrient deficiency ; Oncology ; Overexpression ; Oxidative stress ; Peripheral blood ; RNA-directed DNA polymerase ; Rodents ; Senescence ; Stem cells ; Telomerase ; Telomerase - genetics ; Telomerase - metabolism ; Telomerase reverse transcriptase ; Telomere - genetics ; Telomere Shortening - genetics ; Telomere Shortening - physiology ; Telomeres ; Transgenic animals ; Transgenic mice ; Trends</subject><ispartof>PloS one, 2013-01, Vol.8 (1), p.e53760-e53760</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Vera et al. 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In addition, depending of the genetic background, CR can also increase or decrease mouse longevity. This has highlighted the importance of identifying the molecular pathways that interplay with CR in modulating longevity. Significant lifespan extension in mice has been recently achieved through over-expression of the catalytic subunit of mouse telomerase (mTERT) in a cancer protective background. Given the CR cancer-protective effects in rodents, we set to address here whether CR impacts on telomere length and synergizes with mTERT to extend mouse longevity. CR significantly decreased tumor incidence in TERT transgenic (TgTERT) mice and extended their lifespan compared to wild-type (WT) controls under the same diet, indicating a synergy between TgTERT and CR in increasing mouse longevity. 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These results demonstrate that CR attenuates telomere erosion associated to aging and that synergizes with TERT over-expression in increasing "health span" and extending mouse longevity.</description><subject>Age</subject><subject>Aging</subject><subject>Aging - genetics</subject><subject>Aging - physiology</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biology</subject><subject>Biomarkers - metabolism</subject><subject>Body Weight - genetics</subject><subject>Body Weight - physiology</subject><subject>Caloric Restriction</subject><subject>Cancer</subject><subject>Catalysis</subject><subject>Cell division</subject><subject>Chromosome Aberrations</subject><subject>Chromosomes</subject><subject>Deoxyribonucleic acid</subject><subject>Diabetes</subject><subject>Dietary restrictions</subject><subject>Disease</subject><subject>DNA</subject><subject>Elongation</subject><subject>Food intake</subject><subject>Genetic engineering</subject><subject>Health</subject><subject>Humans</subject><subject>Leukocytes</subject><subject>Life span</subject><subject>Longevity</subject><subject>Longevity - 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In addition, depending of the genetic background, CR can also increase or decrease mouse longevity. This has highlighted the importance of identifying the molecular pathways that interplay with CR in modulating longevity. Significant lifespan extension in mice has been recently achieved through over-expression of the catalytic subunit of mouse telomerase (mTERT) in a cancer protective background. Given the CR cancer-protective effects in rodents, we set to address here whether CR impacts on telomere length and synergizes with mTERT to extend mouse longevity. CR significantly decreased tumor incidence in TERT transgenic (TgTERT) mice and extended their lifespan compared to wild-type (WT) controls under the same diet, indicating a synergy between TgTERT and CR in increasing mouse longevity. In addition, longitudinal telomere length measurements in peripheral blood leukocytes from individual mice showed that CR resulted in maintenance and/or elongation telomeres in a percentage of WT mice, a situation that mimics telomere dynamics in TgTERT cohorts. These results demonstrate that CR attenuates telomere erosion associated to aging and that synergizes with TERT over-expression in increasing "health span" and extending mouse longevity.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23349740</pmid><doi>10.1371/journal.pone.0053760</doi><tpages>e53760</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Age Aging Aging - genetics Aging - physiology Animals Apoptosis Biology Biomarkers - metabolism Body Weight - genetics Body Weight - physiology Caloric Restriction Cancer Catalysis Cell division Chromosome Aberrations Chromosomes Deoxyribonucleic acid Diabetes Dietary restrictions Disease DNA Elongation Food intake Genetic engineering Health Humans Leukocytes Life span Longevity Longevity - genetics Longevity - physiology Longitudinal Studies Male Malnutrition Mammals Medical research Medicine Metabolism Mice Mice, Inbred C57BL Mice, Transgenic Nutrient deficiency Oncology Overexpression Oxidative stress Peripheral blood RNA-directed DNA polymerase Rodents Senescence Stem cells Telomerase Telomerase - genetics Telomerase - metabolism Telomerase reverse transcriptase Telomere - genetics Telomere Shortening - genetics Telomere Shortening - physiology Telomeres Transgenic animals Transgenic mice Trends |
| title | Telomerase reverse transcriptase synergizes with calorie restriction to increase health span and extend mouse longevity |
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