A strategy for the ubiquitous overexpression of human catalase and CuZn superoxide dismutase genes in transgenic mice.
Ubiquitous overexpression of CuZn superoxide dismutase does not extend life span in mice.
Gene therapy for the hemoglobin disorders.
Mech Ageing Dev 2003 Feb;124(2):219-27.
A strategy for the ubiquitous overexpression of human catalase and CuZn superoxide dismutase genes in transgenic mice.
Chen X, Mele J, Giese H, Van Remmen H, Dolle ME, Steinhelper M, Richardson A, Vijg J.
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 78229, San Antonio, TX, USA.

In the present study, we generated transgenic mice that overexpress catalase or CuZn superoxide dismutase (CuZnSOD) in all tissues using large genomic DNA fragments. An 80 kb human genomic DNA, containing the 33 kb human CAT gene as well as the 41 kb of 5' and the 6 kb of 3' flanking regions, was obtained by screening a human P1 library and was used to produce transgenic mice Tg(CAT). Transgenic mice Tg(SOD1) were produced by a similar strategy using a 64 kb human genomic DNA containing the 10 kb human SOD1 gene and the 27 kb of both 5' and 3' flanking regions. Catalase mRNA levels were 2-6- fold higher and catalase activity levels were 2-4- fold higher in the various tissues of the hemizygous Tg(CAT) mice compared with wild type mice. The mRNA levels for CuZnSOD were 2-12- fold higher and the CuZnSOD activity levels were 2-5- fold higher in the hemizygous Tg(SOD1) mice compared with wild type mice. In summary, our study demonstrates that a strategy of using large genomic DNA containing either the entire human CAT or SOD1 gene with large flanking regions gives ubiquitous increased _expression of CuZnSOD and catalase. In addition, the _expression of catalase closely reflects the tissue specific pattern found in the endogenous gene. These transgenic mice will be useful in studying the role of oxidative stress/damage in aging and age-related pathologies.


J Gerontol A Biol Sci Med Sci 2000 Jan;55(1):B5-9.
Ubiquitous overexpression of CuZn superoxide dismutase does not extend life span in mice.
Huang TT, Carlson EJ, Gillespie AM, Shi Y, Epstein CJ.
Department of Pediatrics, University of California, San Francisco 94143-0546, USA.

Oxidative damage has been implicated in the aging process and in a number of degenerative diseases. To investigate the role of oxygen radicals in the aging process in mammals, the life spans of transgenic mice on a CD-1 background expressing increased levels of CuZn superoxide dismutase (CuZnSOD), the enzyme that metabolizes superoxide radicals, were determined. Homozygous transgenic mice with a two- to five-fold elevation of CuZnSOD in various tissues showed a slight reduction of life span, whereas hemizygous mice with a 15- to 3-fold increase of CuZnSOD showed no difference in life span from that of the nontransgenic littermate controls. The results suggest that constitutive and ubiquitous overexpression of CuZnSOD alone is not sufficient to extend the life spans of transgenic mice.


Curr Hematol Rep. 2003 Jul;2(4):348-55.
Gene therapy for the hemoglobin disorders.
Persons DA, Nienhuis AW.
St. Jude Children's Research Hospital, 332 North Lauderdale Drive, Memphis, TN 38105, USA.

The hematologic disorders of beta-thalassemia and sickle cell disease are the most prevalent of human genetic diseases. Although palliative therapies and curative stem cell transplantation therapy have been developed for these disorders, treatment still remains suboptimal and many patients suffer significant morbidity and early mortality. Therefore, development of a gene therapy approach has been sought for many years. Major progress in the globin gene therapy field has been achieved by several laboratories. Using lentiviral vectors to obtain high-level _expression of complex globin gene cassettes, therapeutic correction of several murine models of beta-thalassemia, and sickle cell disease was recently reported. This progress, coupled with developments in the ability to select and expand genetically modified stem cells in vivo, has advanced the possibility of gene therapy for the hemoglobin disorders in the near future. We review the developments in several areas that are critical for successful gene therapy of the hemoglobin disorders.

on the Adriatic Coast
The Anti-Aging Fasting Program consists of a 7-28 days program (including 3 - 14 fasting days). 7-28-day low-calorie diet program is also available .
More information
    The anti-aging story (summary)
Introduction. Statistical review. Your personal aging curve
  Aging and Anti-aging. Why do we age?
    2.1  Aging forces (forces that cause aging
Internal (free radicals, glycosylation, chelation etc.) 
External (Unhealthy diet, lifestyle, wrong habits, environmental pollution, stress, poverty-change "poverty zones", or take it easy. etc.) 
    2.2 Anti-aging forces
Internal (apoptosis, boosting your immune system, DNA repair, longevity genes) 
External (wellness, changing your environment; achieving comfortable social atmosphere in your life, regular intake of anti-aging drugs, use of replacement organs, high-tech medicine, exercise)
    2.3 Aging versus anti-aging: how to tip the balance in your favour!
    3.1 Caloric restriction and fasting extend lifespan and decrease all-cause mortality (Evidence)
      Human studies
Monkey studies
Mouse and rat studies
Other animal studies
    3.2 Fasting and caloric restriction prevent and cure diseases (Evidence)
Hypertension and Stroke
Skin disorders
Mental disorders
Neurogical disorders
Asthmatic bronchitis, Bronchial asthma
Bones (osteoporosis) and fasting
Arteriosclerosis and Heart Disease
Cancer and caloric restriction
Cancer and fasting - a matter of controversy
Eye diseases
Chronic fatigue syndrome
Sleeping disorders
Rheumatoid arthritis
Gastrointestinal diseases
    3.3 Fasting and caloric restriction produce various
      biological effects. Effects on:
        Energy metabolism
Lipids metabolism
Protein metabolism and protein quality
Neuroendocrine and hormonal system
Immune system
Physiological functions
Reproductive function
Cognitive and behavioral functions
Biomarkers of aging
    3.4 Mechanisms: how does calorie restriction retard aging and boost health?
        Diminishing of aging forces
  Lowering of the rate of gene damage
  Reduction of free-radical production
  Reduction of metabolic rate (i.e. rate of aging)
  Lowering of body temperature
  Lowering of protein glycation
Increase of anti-aging forces
  Enhancement of gene reparation
  Enhancement of free radical neutralisation
  Enhancement of protein turnover (protein regeneration)
  Enhancement of immune response
  Activation of mono-oxygenase systems
  Enhance elimination of damaged cells
  Optimisation of neuroendocrine functions
    3.5 Practical implementation: your anti-aging dieting
        Fasting period.
Re-feeding period.
Safety of fasting and low-calorie dieting. Precautions.
      3.6 What can help you make the transition to the low-calorie life style?
        Social, psychological and religious support - crucial factors for a successful transition.
Drugs to ease the transition to caloric restriction and to overcome food cravings (use of adaptogenic herbs)
Food composition
Finding the right physician
    3.7Fasting centers and fasting programs.
  Food to eat. Dishes and menus.
    What to eat on non-fasting days. Dishes and menus. Healthy nutrition. Relation between foodstuffs and diseases. Functional foods. Glycemic index. Diet plan: practical summary. "Dr. Atkins", "Hollywood" and other fad diets versus medical science

Bread, cereals, pasta, fiber
Glycemic index
Meat and poultry
Sugar and sweet
Fats and oils
Dairy and eggs
Nuts and seeds
Food composition

  Anti-aging drugs and supplements
    5.1 Drugs that are highly recommended
      (for inclusion in your supplementation anti-aging program)
        Vitamin E
Vitamin C
Co-enzyme Q10
Lipoic acid
Folic acid
Flavonoids, carotenes
Vitamin B
Vinpocetine (Cavinton)
Deprenyl (Eldepryl)
    5.2 Drugs with controversial or unproven anti-aging effect, or awaiting other evaluation (side-effects)
        Phyto-medicines, Herbs
      5.3 Drugs for treatment and prevention of specific diseases of aging. High-tech modern pharmacology.
        Alzheimer's disease and Dementia
Immune decline
Infections, bacterial
Infections, fungal
Memory loss
Muscle weakness
Parkinson's disease
Prostate hyperplasia
Sexual disorders
Stroke risk
Weight gaining
    5.4 The place of anti-aging drugs in the whole
      program - a realistic evaluation
    6.1 Early diagnosis of disease - key factor to successful treatment.
      Alzheimer's disease and Dementia
Cataracts and Glaucoma
Genetic disorders
Heart attacks
Immune decline
Infectious diseases
Memory loss
Muscle weakness
Parkinson's disease
Prostate hyperplasia
Stroke risk
Weight gaining
    6.2 Biomarkers of aging and specific diseases
    6.3 Stem cell therapy and therapeutic cloning
    6.4 Gene manipulation
    6.5 Prosthetic body-parts, artificial organs
Bones, limbs, joints etc.
Heart & heart devices
    6.6 Obesity reduction by ultrasonic treatment
  Physical activity and aging. Experimental and clinical data.
        Aerobic exercises
Weight-lifting - body-building
Professional sport: negative aspects
  Conclusion: the whole anti-aging program
    9.1 Modifying your personal aging curve
      Average life span increment. Expert evaluation.
Periodic fasting and caloric restriction can add 40 - 50 years to your lifespan
Regular intake of anti-aging drugs can add 20-30 years to your lifespan
Good nutrition (well balanced, healthy food, individually tailord diet) can add 15-25 years to your lifespan
High-tech bio-medicine service can add 15-25 years to your lifespan
Quality of life (prosperity, relaxation, regular vocations) can add 15-25 years to your lifespan
Regular exercise and moderate physical activity can add 10-20 years to your lifespan
These approaches taken together can add 60-80 years to your lifespan, if you start young (say at age 20). But even if you only start later (say at 45-50), you can still gain 30-40 years

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    9.2 The whole anti-aging life style - brief summary 
    References eXTReMe Tracker
        The whole anti-aging program: overview

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