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ANTI-AGING BIOMEDICINE.
HIGH TECH BIO-MEDICAL TECHNOLOGIES FOR DISEASE TREATMENT AND LIFE EXTENSION.
EXPERIMENTAL AND CLINICAL DATA.

 
 6.3 STEM SELL THERAPY, CLONING, REGENERATIVE MEDICINE 
   
 
Stem cell therapies: a tale of caution.
Bone-marrow-derived cells contribute to glomerular endothelial repair in experimental glomerulonephritis.
Human embryonic or adult stem cells: an overview on ethics and perspectives for tissue engineering.
Stem cells and cardiovascular disease.
Current status and perspectives of stem cell therapy for the treatment of
diabetes mellitus.
 
Stem cell therapy

Replacement organ tissues engineering.

In the future, if you get in an accident and you lose a kidney, we'll take a skin cell and we'll grow you up a new one. This is not science fiction.

In the future, tissue engineering and stem cell science will allow us to cure disease, regenerate body parts, even delay death. Such is the vision of ROBERT LANZA, the chief scientific officer at Advanced Cell Technology, a Massachusetts biotech firm that is a leader in developing cell-based therapies. The recent discovery that an engineered virus can restore an adult cell to its youthful condition by altering just a handful of genes—a technique called cellular reprogramming—brings his futuristic medical goals a bit closer to reality.

What is so significant about the new technique of cellular reprogramming? You're turning a terminally differentiated cell back in time to make it what's called an induced pluripotent stem cell. "Pluripotent" means it can become all the cell types in the body. Induced pluripotent stem cells are not controversial at all because you don't use embryos or cloning. You can take a skin cell from you, me, or anybody, and then introduce factors [proteins that initiate DNA transcription] into the cell that will turn it into a pluripotent cell. You can also introduce the cells into an embryo and they can contribute to the germline and be passed on to subsequent generations.

How could cell-based therapies help us create and transplant new organs?
The two hurdles for transplantation therapy in the last several decades have always been the shortage of cells and tissues, and rejection. Embryonic stem cells solve the supply problem, allowing you to generate an unlimited supply of cells. The problem that has not been solved is rejection, and that's where cloning or this new technology of cellular re-programming comes in—you are using the patient's own tissue.

What diseases do you expect to see treated with cellular therapies?
We recently published a paper on a type of cell we created called a hemangioblast, which exists only transiently in the embryo. With the ability to become all of the blood cells-including your immune cells, red blood cells, all of your blood system, as well as vascu-lature—hemangioblasts have been one of biology's holy grails. The point is, we can use transient, intermediate cells like hemangioblasts as a toolbox to fix the adult body so you don't have to amputate limbs from vascular disease, so you may not have to go blind, or so we can prevent heart attacks. We discovered that you can generate literally millions, or even billions, of these from human embryonic stem cells. No one had ever done that before. Then the question was "Okay, this is great. We got a cell in a petri dish. But what does it do? What can it do?"

Ischemia is what causes people with diabetes to lose limbs—because of the lack of blood, you lose toes, fingers, everything. Malcolm Moore at Memorial Sloan-Kettering Cancer Center has an animal model of ischemia. In these animals, if the femoral vein is severed, there is very minimal blood flow, like 10 to 20 percent. We injected hemangioblasts into the muscle of the damaged ischemic limb in a group of these animals. Within a month we found almost 100 percent restoration of the blood flow. I certainly wouldn't have expected that. I thought these cells were pretty amazing, but not that amazing.

You are also looking at growing blood from reprogrammed cells, right?
The military is concerned about a real crisis they may face. They don't have enough O-negative blood, the type that can be accepted by anyone who needs a transfusion. There is often not enough time for tissue matching in the battlefield environment. In the past they have had severe shortages and have had to fly in O-negative blood from Germany and other countries. They would like to build a machine they can put on a Humvee that will make all the blood they want. Now we can make literally 10 to 100 billion red blood cells from one little six-well plate. We're learning how to make platelets, to be used for clotting, for anyone in an emergency situation that needs to stop bleeding. That could have tremendous value.

We share the first floor of our building with the American Red Cross. Every day they have their signs out on the road looking for blood donors: "Urgent need for blood." In a few years, hopefully all they will need to do is simply say, "Okay, we're running low, make us up 100 units."

Will it be possible to engineer an entire new body part?
To realize the full potential of stem cells, we must learn how to reconstitute them into more complex tissues and structures. If we want to make an artery or bones or even an entire kidney or a heart, we need to learn to assemble and grow them on a biodegradable scaffold that the body can later absorb. You let the cells grow, and when you put them back in the body, the body reabsorbs the synthetic materials that are biodegradable and you're left only with the living tissue.

In the future, if you get in an accident and you lose a kidney, we'll take a skin cell and we'll grow you up a new one. This is not science fiction. The field is moving so fast that by the time anyone who is middle-aged or younger now is older, we will simply grow you a new kidney. What seems like science fiction and space age is going to become reality really quickly.

What about life span? Will these cells help us live longer?
If you look at the turn of the last century, peopie's life span was, on average, about 36. It is now double that. It turns out that human longevity plateaus as it approaches around 120 years—that is probably the maximum. Certainly by eliminating infectious diseases and some of the chronic diseases such as cancer, we can get over 100. What we're talking about is patching you back together like a bicycle tire up to 120 years. That was always my thinking. But now with these heman-gioblasts, I have questioned my own rules. These hemangioblasts can go in and fix the damaged tissue.

So, okay, you patch the body together, but then you're going to become senile. Now we're learning that we may be able to repair the damage in the brain itself, too. If this continues the way it looks like it's going, we may break that ceiling, like breaking the sound barrier. I'd be very hesitant to put a lid as to where longevity's going to go.

Article by PAMELA WEINTRAUB from Discover magazine (Summer 2009).



Stem cells enable recovery from spinal injury

Paralysed rats have been enabled to walk again, by transplanting nerve cells derived from human embryonic stem cells into the animals. The findings add to a growing number of studies that suggest that embryonic stem cells could have a valuable role to play in treating spinal injuries. The researchers say trials on people using this technique could start in about two years time. Researchers are exploring a number of approaches to enable recovery from spinal-cord injury, including drugs that overcome spinal cells' reluctance to re-grow, ways of bridging the gap between severed nerves, and transplants of various tissues, including adult stem-cells derived from bone marrow, and nerve cells from the nose. Human trials of some treatments, such as that using nose cells, have already begun. But the first stem-call trials will be on patients
with recent spinal cord injuries and localised damage; treating people who have been paralysed for years, or who suffer from degenerative nerve diseases, is more difficult.
Ways will also have to be found to prevent people rejecting the stem cells. One possible alternative to immunosuppressant drugs would be to first give the patient bone-marrow stem cells from the same source as the nerve cells. This might trick the patient’s immune system into developing tolerance.

Limitations

But adult cells have serious limitations as a mass-market treatment, because not many cells can be grown from a single source. That is not a problem with embryonic stem cells (ESCs). "One cell bank derived from a single embryo produces enough neurons to treat 10 million Parkinson's disease patients", says Thomas Okarma of the Geron company in California. What is more, adult stem cells may not be as versatile. "At this moment, there is very little hard evidence that a bone marrow stem cell can turn into anything but blood, or that a skin stem cell can become anything but skin", he says. ESCs, on the other hand, have the potential to develop into practically any type of tissue.But there is nevertheless a serious problem with ESCs. "Undifferentiated human embryonic stem cells have a very high probability of forming tumours," says Hans Keirstead at the University of California, Irvine, whose team has performed the latest research. To prevent this, his team turned ESCs into specialised cells before transplanting them. They transformed the ESCs into oligodendrocytes, the cells that form the insulating layer of myelin that is vital for conducting nerve impulses. Keirstead's team transplanted the oligodendrocytes into rats with "bruised" spines. After nine weeks, the rats fully regained the ability to walk, he says, whereas rats given no therapy remained paralysed. The team repeated the experiment on three separate occasions, with the same results. Analysis of the rats' spinal cords revealed that the transplanted oligodendrocytes had wrapped themselves around neurons and formed new myelin sheaths. The transplanted cells also secreted growth factors that appear to have stimulated the formation of new neurons.While many promising spinal repair experiments have proved hard to reproduce, researchers at Johns Hopkins University in Baltimore, Maryland, also announced similar results last week. The team injected undifferentiated human ESCs into rats with injured spinal cords. After 24 weeks, the treated rats could support their own weight. Team leader Douglas Kerr thinks the animals' recovery was not due to the growth of new cells, but to the secretion of two growth factors (TGF-alpha and BDNF), which protected damaged neurons and helped them to re-establish connections with other neurons. "The stem cells' magic was really their ability to get into the area of injury and snuggle up to those neurons teetering on the brink of death," says Kerr, whose results will appear in the Journal of Neuroscience.
" Umbilical cord blood stem cells are used as a part of the therapy regimen for nearly 50 diseases today. One of the challenges in developing additional cellular therapies is the need to multiply and preserve large quantities of these powerful umbilical cord blood stem cells for use in treating an even broader range of diseases. These important studies indicate that we can substantially increase the number of these valuable cells and freeze them for later use", says Jan Visser of ViaCell.

Policy on regulation and funding of research

Okarma hopes the results will help persuade policy makers in Washington not to ban therapeutic cloning, which is one way of obtaining human ESCs, and increase funding for ESC research. "The promise of this technology is beginning to be realised", he says. "That's why we think this battle is worth fighting."

 

   
   
Med J Aust. 2003 Aug 4;179(3):164-6.
Stem cell therapies: a tale of caution.
Byrne E, Howells DW.
Centre for Neuroscience, The University of Melbourne, Melbourne, VIC 3010, Australia.

One of the most exciting possibilities in human therapeutics is that stem cells (embryonic or adult) may compensate for cell loss in disease, with functional recovery. This has received considerable publicity in the lay press. Much work remains to be done to turn stem cell therapy into a practical reality for major degenerative diseases, especially those affecting the nervous system. Medical scientists and journalists should work together in ensuring that the general public has a realistic understanding of the likely time frame in which benefits from stem cell therapies will be realised.

   
   

Am J Pathol. 2003 Aug;163(2):553-62.
Bone-marrow-derived cells contribute to glomerular endothelial repair in experimental glomerulonephritis.
Rookmaaker MB, Smits AM, Tolboom H, Van 't Wout K, Martens AC, Goldschmeding R, Joles JA, Van Zonneveld AJ, Grone HJ, Rabelink TJ, Verhaar
MC.

Department of Vascular Medicine, University Medical Center, Utrecht, The Netherlands.

Glomerular endothelial injury plays an important role in the pathogenesis of renal diseases and is centrally involved in renal disease progression. Glomerular endothelial repair may help maintain renal function. We examined whether bone-marrow (BM)-derived cells contribute to glomerular repair. A rat allogenic BM transplant model was used to allow tracing of BM-derived cells using a donor major histocompatibility complex class-I specific mAb. In glomeruli of chimeric rats we identified a small number of donor-BM-derived endothelial and mesangial cells, which increased in a time-dependent manner. Induction of anti-Thy-1.1-glomerulonephritis (transient mesangial and secondary glomerular endothelial injury) caused a significant, more than fourfold increase in the number of BM-derived glomerular endothelial cells at day 7 after anti-Thy-1.1 injection compared to chimeric rats without glomerular injury. The level of BM-derived endothelial cells remained high at day 28. We also observed a more than sevenfold increase in the number of BM-derived mesangial cells at day 28. BM-derived endothelial and mesangial cells were fully integrated in the glomerular structure. Our data show that BM-derived cells participate in glomerular endothelial and mesangial cell turnover and contribute to microvascular repair. These findings provide novel insights into the pathogenesis of renal disease and suggest a potential role for stem cell therapy.

   
   

Adv Exp Med Biol. 2003;534:27-45.
Human embryonic or adult stem cells: an overview on ethics and perspectives for tissue engineering.
Henon PR.
Departement d'Hematologie and Institut de Recherche en Hematologie et Transfusion, Hopitaux de Mulhouse, 87 Avenue d'Altkirch, Mulhouse, France.

Over the past few years, research on animal and human stem cells has experienced tremendous advances which are almost daily loudly revealed to the public on the front-page of newspapers. The reason for such an enthusiasm over stem cells is that they could be used to cure patients suffering from spontaneous or injuries-related diseases that are due to particular types of cells functioning incorrectly, such as cardiomyopathy, diabetes mellitus, osteoporosis, cancers, Parkinson's disease, spinal cord injuries or genetic abnormalities. Currently, these diseases have slightly or non-efficient treatment options, and millions of people around the world are desperately waiting to be cured. Even if not any person with one of these diseases could potentially benefit from stem cell therapy, the new concept of "regenerative medicine" is unprecedented since it involves the regeneration of normal cells, tissues and organs which could allow to treat a patient whereby both, the immediate problem would be corrected and the normal physiological processes restored, without any need for subsequent drugs. However, conflicting ethical controversies surround this new medicine approach, inside and outside the medical community, especially when human embryonic stem cells (h-ESCs) are concerned. This ethical debate on clinical use of h-ESCs has recently encouraged.

   
   

J Nucl Cardiol. 2003 Jul-Aug;10(4):403-12.
Stem cells and cardiovascular disease.
Abbott JD, Giordano FJ.

Several recent discoveries have shifted the paradigm that there is no potential for myocardial regeneration and have fueled enthusiasm for a new frontier in the treatment of cardiovascular disease-stem cells. Fundamental to this emerging field is the cumulative evidence that adult bone marrow stem cells can differentiate into a wide variety of cell types, including cardiac myocytes and endothelial cells. This phenomenon has been termed stem cell plasticity and is the basis for the explosive recent interest in stem cell-based therapies. Directed to cardiovascular disease, stem cell therapy holds the promise of replacing lost heart muscle and enhancing cardiovascular revascularization. Early evidence of the feasibility of stem cell therapy for cardiovascular disease came from a series of animal experiments demonstrating that adult stem cells could become cardiac muscle cells (myogenesis) and participate in the formation of new blood vessels (angiogenesis and vasculogenesis) in the heart after myocardial infarction. These findings have been rapidly translated to ongoing human trials, but many questions remain. This review focuses on the use of adult bone marrow-derived stem cells for the treatment of ischemic cardiovascular disease and will contrast how far we have come in a short time with how far we still need to go before stem cell therapy becomes routine in cardiovascular medicine.

   
   

Med Klin. 2003 May 15;98(5):277-82.
Current status and perspectives of stem cell therapy for the treatment of
diabetes mellitus.

Path G, Seufert J.

Due to autoimmune destruction of insulin-producing pancreatic b-cells, type 1 diabetic patients, and also patients with type 2 diabetes suffering from defective insulin secretion rely on lifelong substitution with insulin. A clinically established alternative therapy for diabetics with exogenous insulin substitution, the transplantation of human islets of Langerhans, is limited by the lack of donor organs. The intensive search for new sources of pancreatic b-cells now focuses on human stem cells. Insulin-producing cells for transplantation can be generated from both embryonic and adult pancreatic stem cells. Both types of stem cells, however, differ with respect to availability, in vitro expansion, potential for differentiation, and tumorigenicity, which is elucidated by the authors. Before stem cell therapeutic strategies for diabetes mellitus can be transferred to clinical application in humans, aspects of functional effectivity, safety, and cost-effectiveness have to be solved. Considering these prerequisites in the Diskuslight of currently available therapeutic options, however, it can be estimated, that stem cell therapy for diabetes mellitus may be cost-effectively introduced into clinical routine in the future.

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FASTING / LOW CALORIE PROGRAMS
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)
        Obesity
Diabetes
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
Allergies
Rheumatoid arthritis
Gastrointestinal diseases
Infertility
Presbyacusis
    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
Radio-sensitivity
Apoptosis
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
     

Vegetables
Fruits
Bread, cereals, pasta, fiber
Glycemic index
Fish
Meat and poultry
Sugar and sweet
Legumes
Fats and oils
Dairy and eggs
Mushrooms
Nuts and seeds
Alcohol
Coffee
Water
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
Selenium
Flavonoids, carotenes
DHEA
Vitamin B
Carnitin
SAM
Vinpocetine (Cavinton)
Deprenyl (Eldepryl)
    5.2 Drugs with controversial or unproven anti-aging effect, or awaiting other evaluation (side-effects)
        Phyto-medicines, Herbs
HGH
Gerovital
Melatonin
      5.3 Drugs for treatment and prevention of specific diseases of aging. High-tech modern pharmacology.
        Alzheimer's disease and Dementia
Arthritis
Cancer
Depression
Diabetes
Hyperlipidemia
Hypertension
Immune decline
Infections, bacterial
Infections, fungal
Memory loss
Menopause
Muscle weakness
Osteoporosis
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
Arthritis
Cancer
Depression
Diabetes
Cataracts and Glaucoma
Genetic disorders
Heart attacks
Hyperlipidemia
Hypertension
Immune decline
Infectious diseases
Memory loss
Muscle weakness
Osteoporosis
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
        Blood
Bones, limbs, joints etc.
Brain
Heart & heart devices
Kidney
Liver
Lung
Pancreas
Spleen
    6.6 Obesity reduction by ultrasonic treatment
  Physical activity and aging. Experimental and clinical data.
        Aerobic exercises
Stretching
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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