What is Aging or Senescence ?         Click for Overview

Aging is the progressive accumulation of diverse, deleterious changes with time that increase the chance of disease and death. Aging is an underlying condition that allows many major human diseases, such as atherosclerosis, cancer, cardiovascular defects, cataract, diabetes, Alzheimer’s [dementia], macular degeneration, neuro-degeneration, osteoporosis and sarcopenia. The optimal solution for improving health in old age is to prevent these age-related diseases by maintenance of cellular functionality by pharmaceutical or nutraceutical intervention. Aging is a ‘process’ where there is a loss of tissue and organ functionality that originates from the reduction in the individual cells’ ability to convert nutrient fuels into cellular energy. As less energy is produced by each cell it is less able to ‘cope’ with cellular maintenance. Oxidative damage occurs, cellular repair mechanisms become less efficient and a cascade towards the demise of each cell progresses. As cells die and are not replaced due to the lowered vitality of the stem cell population, the functionality of tissues and organs is compromised and a trend of decline is established.

Do all people and animals age the same ?  Click for overview

The progression and rate of aging is NOT synchronous in tissues nor organs, in organisms within a species, in organs and tissues within an organism, in cell types within a tissue, in sub-cellular compartments within a cell type, nor in macromolecules within a cell. The process of aging is considered as being stochastic and individualistic. Genes, environment and chance appear to act in combination to determine the rate of aging and the longevity of an individual. However, like it or not, humans are living longer. Better nutrition, health care, vaccination, antibiotics, public and residential disinfection, soap and detergents, and waste treatment have essentially eradicated mortality as a consequence of the acute and childhood diseases that once ravaged humanity. The result is that the decline of bodily functionality and the resulting crisis of age-related disease has become a global issue, with the numbers of the older population growing faster than their overall populations of most countries--even developing ones. By the year 2030 almost 20% of the US population, or more than 70-million people, will be past the age of 65. Among the foregoing changes in demographics, one of the most interesting is that percentage-wise, the fastest growing age group of Americans are those over the age of 100. By 2030, there will be 324,000 Americans 100 and older, and by 2050 that number will double

HOW WILL YOUR MIND WORK AFTER 80 ?
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Encouraging though they may seem, however, the increase in life expectancy data harbor inherent problems. Living well past our reproductive prime brings a plethora of consequences, lifestyle changes, disability management, burdens on the healthcare system, public transportation, and government finances and declining independent living status and functionality. It has always been normal to expect to have reduced physical capabilities as we pass through the years. Most Americans expect that an extended longevity will be a reality during their lifetime. The expectation is that we all can live to, and past, 100 years old, in good health and having an independent living status. No-one hopes to have to rely upon their relatives, or the government, for assistance in any period of their lives. However, the stats show that about 50% of all Americans will lose their minds to a neuro-pathologic disease and/or dementia as they age past 80. The data shows that Alzheimer's disease symptoms will afflict one half of all living individuals at this time of life. Don't believe it ? See published data. SEE INFO on Alzheimer's. They are real, disturbing, and, of course, not published much. What will an extended life mean to you if you don't have a functioning mind ?? Not much I bet, we have all seen the wonderful life of the animals, especially primates, in a Zoo.

The decline to be ‘expected’ in the aged.
PIX  SKIN,  BRAIN, MUSCLE  PERFORMANCE,  HORMONE LEVELS. Click

As the years pass people are looking to adopt strategies for avoiding the chronic diseases and the accumulation of daily discomforts and disabilities that threaten to intrude on their lifestyle. They may simply term these ailments--often consisting of cartilage and bone loss, enlargement of the prostate and heart, obesity, diminished immunity and libido, sleep disorders, and depression--“ lack of energy.” However, attendant are the chronic diseases such as Alzheimer’s, osteoarthritis, cardiovascular disease, diabetes, and cancer. Few people are aware that the symptoms are universal and the consequence a lack of energy at the cellular level. According to the principles of aging and longevity our bodies have developed as a consequence of millions of years of evolution, and so the age-related physiological decline after adulthood, and the onset of ailments and disease before eventual death are considered the ‘normal’ sequence of events. In the case of a disease, such as a cancer of any specific kind, therapy, ideally, means the removal and elimination of the cancer cells and restoration of the affected organ/tissue to its original disease-free state. Aging is a condition, a stage in the process of growth and change of the body ! Aging must NOT be considered as a disease. Trying to cure this multifaceted condition as a disease is unscientific and misguided. The viewpoint of aging [senescence] as condition that represents the declining stage of growth and development makes intervention in the aging process a radically different problem and concern than the treatment of specific diseases. Retarding aging must slow or reverse the ‘process’. We must re-activate the genetic developmental and/or ‘protective’ processes that led to our body’s adulthood status. Scientific and rational anti-aging strategies must aim to slow down the aging process, to restore the ’adulthood’ or ‘youthful’ repair and maintenance mechanisms of the cells and tissues and thereby prevent and/or delay both the physiological decline and strengthen us against inherent ‘aging’ diseases, and to regain lost functional abilities. To maintain health and functionality requires that these strategies aim at the root molecular causes of the underlying aging process and modulate these causes so that the period of healthful, functional, independent existence is extended.

Aging Research!  What has been done and discovered ? Click

SEE INFO Slideshow-Alzheimer

Alzeimer's Disease          Live long enough and its yours!   Click

Alzheimer's Disease. An estimated 25-29 million people in the world suffer from dementia… either cardiovascular dementia [insufficient blood supply to the brain] or Alzheimer’s disease. Alzheimer’s induced dementia, and other cognitive impairments, mean a significant memory impairment and loss of intellectual functionality. Symptoms are: Forgetfulness, mood swings and behavioral changes Language problems and execution of other familiar activities Changes in spatial and temporal orientation Impaired judgment and abstract thinking Personality changes combined with a loss of initiative. No-one wants to live with a dysfunctional brain or without the ability to think clearly. These symptoms prevail in the majority of dementia cases. Over the next century, the World Health Organization experts estimate that Alzheimer’s disease will be more prevalent than AIDS, cancer, and all cardiovascular diseases. Why? Because as people are living longer and age-related neural impairment will surface as a major deterioration that parallels the length of time a person has been alive. AND we will have more and more people past the age of 85. The National Center for Health Statistics reports that Alzheimer’s disease is the 12th cause of death in the United States and the 8th cause for those 65 and older. The statistics show that after 65 year old about 10% of humans have symptoms of Alzheimer’s while 20% are victims after 75; AND AFTER 85 one half of all Americans have Alzheimer’s. The loss of the mind is unexpected and unacceptable. ‘aging condition’; as the years pass a deterioration of the brain parallels the decay of the body. In fact, surveys show that people fear the incapacity of the brain more than the loss of physical performance which they have expected since youth. The therapeutic retardation of human aging is a multi-billion dollar market. Additionally extending the healthy lifespan of our pets is a lucrative and readily accessible market. During the past few decays scientists have recognized that nutrition is one of the keys to a longer healthy existence and nature provides many substances that are beneficial to along health life. There are naturally occurring, purified compounds that enhance our brain function, another that retards and reverses symptoms of Alzheimer’s, others that improve our energy metabolism and actually increase the capability for daily movement and activity in the elderly. In the event of a stroke, the ischaemic damage that occurs in the brain can be dramatically reduced by administering natural compounds. The role of the pharmaceutical companies is to modify some of these compounds, improve on them both in efficacy and reduction of side effects and, of course, in the process make money by making the new derivatives available to the public as well as to the animal care marketplace.

Alzheimer's Medical Treatments.  'Relief NOT Cure'       Click here to View Summary

QUOTE T.S. Anekonda, P.H. Reddy / Brain Research Reviews 50 (2005) 361– 376 “Currently available FDA-approved drugs treat AD {Alzheimer’s} symptomatically and provide temporary relief from dementia. However, these drugs have adverse drug effects and do not cure the disease. There remains an urgent need for developing alternative approaches to AD therapeutics. ’ ……‘ There are only four drugs that the FDA has approved and that are currently available for treating AD patients in the United States. Tacrine (CognexR), Donepezil (AriceptR), and Rivastigmine (ReminylR)—inhibit acetylcholinesterase (AChEI). Memantine (NamendaR), the most recently approved drug, inhibits N-methyl-D-aspartate [NMDA] receptors, prevents glutamate excitotoxicity, and shows minimal adverse drug effects in AD patients. All four of these drugs improved the cognitive functions of AD patients symptomatically and have thus improved the quality of life for these patients; however, these drugs do not modify the disease mechanism in the long run. Thus, when patients no longer take the drugs, their symptoms of AD return. The paucity of drugs currently available for treating AD and their limited targets in AD pathology call for the development of a new generation of drugs that target other cellular pathways in AD pathogenesis.”

Growth Hormone.        Click

Growth Hormone. The decline in natural Growth Hormone secretion- a deficiency, contributes to bodily decay as you age. Growth hormone secretion formula. Growth hormone secretion can be increased by an oral intake of 500 milligrams of acetyl-L-carnitine (ALCAR) together with between 10 and 30 milligrams of L-ornithine immediately before going to sleep in the evening. Aging humans and animals they suffer from 1.) a decrease in energy production and because of this decline….. 2.) a slow down in the rate of maintenance and repair of the components of our cells, tissues and body. The known ways to increase growth hormone secretion are by 1.] direct injection of the hormone, 2.] administration of a brain hormone secretagogue [releasing factor] or 3.] by nutritionally stimulating growth hormone secretion. The functionality of cells and tissue components declines with age. This decline is mostly due to oxidation damaged of cellular membranes, lipids and proteins that are not easily replaced. See. the protein synthesis vs. oxidative damage. The five-fold decline in the rate of secretion of growth hormone over life span is a huge contributing factor to these detrimental processes. Growth hormone is responsible for adolescent growth. We now understands that cells and tissues require this hormone at all times throughout life. Growth hormone and Insulin are the central hormones that promote energy production and proteins synthesis in cells. Nutrients, carbohydrates and fats in the diet are not enough, cellular stimulation by growth hormone is required for metabolism and conversion of all foods into ‘usable’ cellular energy. In healthy, aging humans the level of insulin stimulation of cells changes little, but growth hormone levels decline five-fold. A fact that is reflected in reduced muscle strength and athletic performance, increased abdominal fats, changed body composition and a general lack of energy. SEE INFO on Alzheimer's. Older individuals can increase muscle mass, sleep better, increase bone density, improve immune system protection, and feel better [4] when given injections of recombinant growth hormone. Unfortunately, growth hormone injections are very expensive, and the delivery method - bolus injection, suppresses the natural growth hormone release. Also oral spray absorption techniques do not allow fine tuned control of delivery. A simple way to elevate your Growth Hormone level. At less than $1/day a mixture that gently and controllably increases your own natural growth hormone release is available; it involves oral intake of two natural (very safe) supplements found in your body. Acetyl-carnitine and Ornithine. The patented formulation is a mixture of two supplements that are available in health food stores. The supplement mixture works - and after you try it, you will ‘feel’ that it works. You can make up the mixture by yourselves. However, you must be careful with the levels and ratios. Sale of the patented mixture is not allowed. The stimulation of growth hormone in a controlled manner will help you temper the gradual decline in 'maintenance capabilities' of our bodies. Aging damage is very gradual period of "Managed Decline" but, in humans, the decline seriously accelerates to "Accelerated Failure" after 60-65 years old, from insufficient maintenance and during this period a wide variety of age-related diseases rapidly appear. The stimulation of growth hormone is one step that can help postpone the "Managed Decline" phase and halt the progression to the "Accelerated Failure" phase. Aging is a progression of the body from ‘Managed Decline’ to ‘Accelerated Failure’. May GOD be with you. After humans reach adulthood, a slow ‘managed decline’ of function takes place in the body. This gradual decline continues because of minimal repair and maintenance, followed by ‘acceleration toward failure’. The decline is due, in part, to the decline in Growth Hormone stimulation of cells and tissues as humans age. As we move into "Accelerated Failure", a very wide variety of diseases become more common, cancer, cardiovascular conditions, arthritis, osteoporosis, etc, etc. . The increase in the wide variety of diseases that accompany age is a consequence of the decline in cellular energy metabolism and ‘Maintenance Capability’. Piecemeal treatment of each age-related disease will not ward off this process. However, we can discourage the propensity for these diseases by the consumption of specific nutrients and supplements. If you don’t believe this you get to die.! It takes time, a lifetime, to get old, so improving your health in less than a year with supplements and nutrients is a significant accomplishment; not to be discounted, the alternative is a more rapid path towards death. Naturally, if you have any medical problems, you must consult with your physician before even considering solutions. Medical doctors are trained to give you any medical suggestions. The supplement and nutrient formula to raise growth hormone levels consists of two parts: 1.) a nutrient composition to increase your natural growth hormone output and 2.) a safeguard against stimulation of cell divisions by intake of bioflavonoids or polyphenols a few hours after each large meal. This is a balanced system, designed to maximize benefit and minimize risk. DON’T DO ONE WITHOUT THE OTHER. Growth hormone secretion formula. Growth hormone secretion can be increased by an oral intake of 500 milligrams of acetyl-L-carnitine (ALCAR) with between 10 and 30 milligrams of L-ornithine. The level of L-ornithine is critical, necessary and MUST be carefully measured. Pre-menopausal women may take this mixture between meals in the morning, before eating. Men and post-menopausal women should take this mixture just before going to sleep at night at least 3 hours after eating. Food will compete with uptake of these nutrients and prevent growth hormone elevation. Pre-menstrual women are slightly more sensitive to the amount of L-ornithine, and should take 10-25 milligrams of L- ornithine (with ALCAR). It is suggested as a starting point of 25 milligrams of L-ornithine and 500 milligrams of acetyl-L-carnitine. The level can be adjusted up or down by your response (more or less), but not more than 30 milligrams of L-ornithine. Your health will not improve by taking more, it may even cause injury. You cannot hurry the gradual process of return to healthier status, it took years to become old, it takes time to reverse most of the physiologic declines of age. “Nothing beautiful ever hurries.” Life is beautiful, hurrying is a fallacy, a mistake, just like the fastlane. GROWTH HORMONE IS A CELL STIMULANT, therefore, controls must be in place. !

Integrins are a series of cell-surface proteins which mediate a variety of cellular processes, such as migration, differentiation, signaling, and death. Integrins in cancerous cells have been identified as major cancer therapy targets due to their role in the spread of metastic colonies and resistance to normal cell death signals. All of these processes are controlled through interaction by integrins with proteins present in the extracellular matrix (ECM) surrounding the cell. The putative amino acid motif for recognition of integrins by ECM proteins is the arginine-glycine-aspartate (RGD) sequence. Therefore, focus has been placed on the use of this motif in the development of new cancer therapeutics for inhibiting integrin interactions which are defective to normal cell life. Our work proposes to synthesize and evaluate new peptide variants based from previously reported peptide sequences. Solid-phase peptide synthesis (SPPS) will be used to vary the acidic and basic sites in the RGD peptide templates to create a series of new peptide-based cancer therapeutics. Electrostatic and hydrogenbonding interactions will be maximized through the inclusion of extended guanidine, phosphate, and sulfonate residues. Mass spectrometric titration and competitive binding studies will be used to evaluate the binding (affinity and selectivity) of our new peptides with: a) synthesized integrin peptide segments representative of the RGD binding domain; and b) intact integrin proteins. Results of mass spectrometric measurements will be correlated with data from other spectroscopic techniques, as well as with data previously published in the literature. This research features a strong synergism between a synthetic (Dr. Ahn) and an analytical (Dr. Schug) chemist. Furthermore, the aims of the proposal are consistent with the expertise of both investigators. Funding of this work will provide the necessary materials for carrying out this research, as well as the necessary preliminary proof-of-principle measurements needed for soliciting further funding. The scope of this research is amenable to extensive further investigations and will be applicable for support by federal agencies, such as the National Institute of Health, the American Cancer Society, and the National Science Foundation.

Why and How of Growth Hormone stimulation
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THE WHY and HOW. We can divide the mechanism of growth hormone secretion question into two: 1.) Why does a mixture of ALCAR and L-ornithine act synergistically (only together, not alone) to cause significant increases in our growth hormone release ? and 2.) How do we get protection by ingestion of bioflavonoids or polyphenols to inhibit cell division? 1.) Why does Acetyl-L-carnitine & L-Ornithine Elevate growth hormone secretion? ALCAR is a lipid transport molecule. Higher cellular levels of ALCAR have regulatory properties that elevate the energy producing capacity of our mitochondria, the energy production parts in our cells. This high level of maximal energy production capability of our cells is typical of youth, then declines with age (Reference 22). This affects our muscles, and every cell in the human body. The level of ALCAR circulating in the blood influences the state of energy production of all tissues, including the brain. When oral supplements of ALCAR is given to old animals, their brain signaling molecules and receptor function increases - almost up to that of a young animal (Reference 23). When you inject very high level of ALCAR into old rats, their maximal energy production (by the mitochondria) is as high a maximal energy production capability as young animals (Reference 24). Thus, when we give 500 milligrams of oral ALCAR just before sleep, we are temporarily boosting the energy capability of cells in our body. This alone will not increase our GH output, but when combined with the L-ornithine it does. In our brain is a monitoring control center called the ‘hypothalamus’. This center determines how much growth hormone the ‘pituitary’ will release. This control is modulated by a opposition between two compounds: somatostatin and growth hormone releasing hormone(GHRH) (Reference 25). While ALCAR is improving the function of this whole tissue, L-ornithine is temporarily inhibiting the release of somatostatin and thus elevating GH release (Reference 26). Thus, at about 1.5 hours and 3 hours after we begin sleep, there is a large release of GHRH which triggers higher levels of GH. This is why you may awaken at 1.5 hours after sleep because your system has just released enough GH to provide much more ‘fat’ fuel. When the body gets more growth hormone, it chooses to burn more fat than glucose, thus increasing the levels of the intermediate acetyl groups that are loaded on to L-carnitine to cause higher blood levels of acetyl-L-carnitine. (GH by its downstream effects, also increases protein synthesis and cell divisions after you eat a meal but not at night when you are fasting.) So we have a feedback system where higher GH release elevates the systemic levels of acetyl-L-carnitine which in turn help support enough GH release. They mutually interact to regulate each other. As we age, the oxidative events that damage our proteins also damage the energy output of our mitochondria and this feeds back via lower blood levels of acetyl-l-carnitine which causes a gradually lessening of the amount of GH released. This, combined with the aging increases in somatostatin production is most of the reason for the gradual but massive decline in GH secretion that we saw in Figure B. This technique is actually fixing what is going wrong, which is why such small changes in the L-ornithine levels are so powerful. This normal aging process causes the continued decline in GH output until a threshold of insufficient repair/replacement changes the situation from a ‘controlled decline’ into an ‘accelerated failure’ that we saw in Figure C. All the diseases that arise in age, except those like cancer, are due to the decline in this maintenance capabilities. When we prevent the maintenance decline, we largely prevent most of that large class of aging diseases. The exception is cancer, which we know arises from DNA damage that removes the controls on division and stimulus for divisions that can be provided by the downstream growth factors generated from GH. We are ‘aging’ in a directed race between 1.) the decline in our maintenance capacities and 2.) the increased mutational rate because of DNA damage that combines with divisions to give us cancer. It is believed that the stimulation of controlled GH release will delay maintenance decline, but would not give protection against cancer. We would be healthier but have a higher incidence of cancer. Therefore….. 2.) Protection against nutritionally-driven cell division [cancer]. There is a need for bioflavonoid/polyphenol protection against unnecessary cell division. Cell division is process in the promotion of cancer. The added advantage of the strong antioxidant and cancer killing properties of these bioflavonoids is even better. This is why we wait 3-5 hours after our major meal before we taking bioflavonoids to ‘shut down the cells’ that are headed for division in ‘division capable’ cells. We are using natures own mechanisms to tilt the playing field for “A Longer Healthy Life” advantage. We can now do this with our longevity as well.

Prosody is the name of linguistic unit for pitch of the voice, stress, length of syllables and other units that are not vowel and consonants. Prosody is a feature of language that is indispensable to achieve good performance in speech understanding and synthesis. Second Language learners and researchers report that unnative-like prosody is the greatest hindrance to being understood by mother tongue speakers. This study of Chinese and English represents a collaboration of the perspectives of linguistics and automatic spoken language processing in extracting, analyzing, and evaluating prosodic categories in large corpora of spoken discourse. We plan to study the syllable-timed and the stress-timed property in the two languages, extract the indicative prosodic features used to signal sentence boundaries, and the impact of tone on intonation. The knowledge gained from this study will be used in the language processing project currently supported by DARPA that translates spoken Chinese to English text. This joint research will offer a unique opportunity for Dr. Liu and Dr. Edmondson to collaborate in three dimensions, as they represent two universities, two departments, and speak two languages, which bring the strength of the two PIs together and allow incorporation of more linguistic knowledge into automatic processing systems.