Telomerase and the Cellular Lifespan: Implications for the Aging Process
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Elizabeth L. Ostler
ABSTRACT
The aging process has multiple causes. However, there is now substantial evidence consistent with the hypothesis that (i) all normal mammalian somatic cells have a finite capacity to replicate and (ii) that gradual cell turnover throughout the lifespan of a mammal eventually exhausts this finite capacity. This results in a gradual accumulation of senescent (irreversibly post-mitotic) cells with increasing age. These cells display a radically different phenotype to their growing counterparts, which has the potential to compromise tissue function. Perhaps the best evidence for this is seen in Werner’s syndrome, a rare genetic disease, in which patients display most of the features of accelerated aging, together with a profoundly compromised replicative lifespan in certain tissue lineages. Several classes of human cells are now known to count divisions by monitoring the progressive attrition of chromosomal ends (telomeres), leading to the activation of a p53-p21waf - dependent G1 checkpoint. Ectopic expression of telomerase has been shown to prevent senescence in several cell types and offers the potential for interventions in the aging process based on tissue engineering, gene therapy or homeografts. However, this telomere-driven senescence mechanism seems to be absent from rodents, which use telomere-independent means (perhaps based upon p14arf) to count divisions. Similar senescence pathways are now being reported in humans, and this, coupled with the demonstration of tissue-specific telomeric loss rates, has the potential to render strategies based on the use of telomerase dependent on the characteristics of the target tissue. Werner’s syndrome may provide strong clues regarding the potential limitations and prospects of such future treatments.
© 2014 by Walter de Gruyter Berlin/Boston
Artikel in diesem Heft
- Titelei
- TABLE OF CONTENTS
- Foreword
- What Happens When Growth Hormone is Discontinued at Completion of Growth? Metabolic Aspects
- Growth Hormone Deficiency and Peak Bone Mass
- Optimal Strategy for Management of Pituitary Disease in the Growth Hormone-Deficient Teenager
- Ethical Dilemmas in Pediatric Endocrinology: Growth Hormone for Short Normal Children
- Evidence-Based Approach to Growth Hormone Replacement Therapy in Adults, with Special Emphasis on Body Composition
- Evidence-Based Growth Hormone Therapy Prediction Models
- New Paradigms for Growth Hormone Treatment in the 21st Century: Prediction Models
- Role of Insulin-like Growth Factor Monitoring in Optimizing Growth Hormone Therapy
- Knockout Mice Challenge Our Concepts of Glucose Homeostasis and the Pathogenesis of Diabetes Mellitus
- Type 2 Diabetes Mellitus in Children: Pathophysiology and Risk Factors
- Emergence of Type 2 Diabetes Mellitus in Children: Epidemiological Evidence
- Treatment of Type 2 Diabetes Mellitus in Children and Adolescents
- Diagnosis of Maturity-Onset Diabetes of the Young in the Pediatric Diabetes Clinic
- Thrifty Genotypes and Phenotypes in the Pathogenesis of Type 2 Diabetes Mellitus
- Estradiol: A Protective Factor in the Adult Brain
- Estrogen Treatment and Estrogen Suppression: Metabolic Effects in Adolescence
- Estrogen, Bone, Growth and Sex: A Sea Change in Conventional Wisdom
- Route-Dependent Endocrine and Metabolic Effects of Estrogen Replacement Therapy
- Telomerase and the Cellular Lifespan: Implications for the Aging Process
- Human Aging and Progeria
- A Role for the Somatotropic Axis in Neural Development, Injury and Disease
- Hypothalamic Growth Hormone-Insulin-like Growth Factor-I Axis across the Human Life Span
- The Lost Voice: A History of the Castrato
- SELECTED POSTER ABSTRACTS
- GROWTH. FETAL GROWTH. SGA
- SYNDROMES: TURNER. PRADER-WILLI. NOONAN. PHP. OTHERS
- GHD. HYPOPITUITARISM. KIGS
- METABOLIC. GENETIC. ADULT. ACROMEGALY
- GH. IGF. IGFBPs
- GROWTH IN SYSTEMIC DISEASE. CRI. RICKETS. STEROIDS
Artikel in diesem Heft
- Titelei
- TABLE OF CONTENTS
- Foreword
- What Happens When Growth Hormone is Discontinued at Completion of Growth? Metabolic Aspects
- Growth Hormone Deficiency and Peak Bone Mass
- Optimal Strategy for Management of Pituitary Disease in the Growth Hormone-Deficient Teenager
- Ethical Dilemmas in Pediatric Endocrinology: Growth Hormone for Short Normal Children
- Evidence-Based Approach to Growth Hormone Replacement Therapy in Adults, with Special Emphasis on Body Composition
- Evidence-Based Growth Hormone Therapy Prediction Models
- New Paradigms for Growth Hormone Treatment in the 21st Century: Prediction Models
- Role of Insulin-like Growth Factor Monitoring in Optimizing Growth Hormone Therapy
- Knockout Mice Challenge Our Concepts of Glucose Homeostasis and the Pathogenesis of Diabetes Mellitus
- Type 2 Diabetes Mellitus in Children: Pathophysiology and Risk Factors
- Emergence of Type 2 Diabetes Mellitus in Children: Epidemiological Evidence
- Treatment of Type 2 Diabetes Mellitus in Children and Adolescents
- Diagnosis of Maturity-Onset Diabetes of the Young in the Pediatric Diabetes Clinic
- Thrifty Genotypes and Phenotypes in the Pathogenesis of Type 2 Diabetes Mellitus
- Estradiol: A Protective Factor in the Adult Brain
- Estrogen Treatment and Estrogen Suppression: Metabolic Effects in Adolescence
- Estrogen, Bone, Growth and Sex: A Sea Change in Conventional Wisdom
- Route-Dependent Endocrine and Metabolic Effects of Estrogen Replacement Therapy
- Telomerase and the Cellular Lifespan: Implications for the Aging Process
- Human Aging and Progeria
- A Role for the Somatotropic Axis in Neural Development, Injury and Disease
- Hypothalamic Growth Hormone-Insulin-like Growth Factor-I Axis across the Human Life Span
- The Lost Voice: A History of the Castrato
- SELECTED POSTER ABSTRACTS
- GROWTH. FETAL GROWTH. SGA
- SYNDROMES: TURNER. PRADER-WILLI. NOONAN. PHP. OTHERS
- GHD. HYPOPITUITARISM. KIGS
- METABOLIC. GENETIC. ADULT. ACROMEGALY
- GH. IGF. IGFBPs
- GROWTH IN SYSTEMIC DISEASE. CRI. RICKETS. STEROIDS
