INTRODUCTION TO ANTI AGING Anti-aging medicine is a clinical specialty is founded on the application of advanced scientific and medical technologies

for the early detection, prevention, treatment, and reversal of age-related dysfunction, disorders, and diseases. It is a healthcare model promoting innovative science and research to prolong the healthy lifespan in humans. As such, anti-aging medicine is based on principles of sound and responsible medical care that are consistent with those applied in other preventive health specialties. The phrase "anti-aging," as such, relates to the application of advanced biomedical technologies focused on the early detection, prevention, and treatment of aging-related disease. Anti-aging medicine complements regenerative medicine, as both specialties embrace cutting-edge biomedical technologies aimed at achieving benefits for both the quality and quantity of the human lifespan. Some of the most promising aspects of regenerative medicine, most notably: Stem cell therapeutics, technologies aiming to beneficially alter the very basic cellular sources of dysfunctions, disorders, disabilities, and diseases Therapeutic cloning, technologies to develop ample sources of human cells, tissues, and organs for use in acute emergency care as well as the treatment of chronic, debilitating diseases Genetic engineering and genomics, advancements that permit the identification and alteration of genetics to ameliorate dysfunctions, disorders, disabilities, and diseases Nanotechnology, deploying micro- and molecular-sized tools to manipulate human tissue biology for microsurgical repair on a gross level, as well as microscopic nano-biology for repair at the most basic cellular level

Taken collectively, the advancements offered by anti-aging and regenerative medicine to improve the quality of, and/or extend the length of, the human lifespan, are the singlemost potent emerging biomedical technologies today. Universally, those involved in healthcare, or those whose fields of expertise intersect with healthcare issues, support anti-aging medicine as a healthcare model promoting innovative science and research to prolong the healthy human lifespan. Public policy organizations and government agencies in a number of nations are now embracing anti-aging medicine as a viable solution to alleviate the mounting social, economic, and medical woes otherwise anticipated to arrive with the trend of unprecedented global aging. Anti-aging medicine is now practiced by thousands of physicians in private medical offices, as well as at some of the most prestigious teaching hospitals around the world. Involving a patient base in the hundreds of thousands worldwide, anti-aging medicine is achieving demonstrable and objective results that beneficially impact the degenerative diseases of aging.

RESEARCH INVOLVING NEURON ANTI AGING

ANTI-AGING RESEARCH UPDATES: SCIENCE LITERATURE Higher-order unfolding of satellite heterochromatin is a consistent and early event in cell senescence. Swanson EC, Manning B, Zhang H, Lawrence JB. J Cell Biol. 2013 Dec 16. Antisense oligonucleotide against GSK-3[beta] improves learning and memory and decreases oxidative stress: implications for Alzheimer disease. Farr SA, Ripley JL, Sultana R, Zhang Z, Niehoff ML, Platt TL, Murphy MP, Morley JE, Kumar V, Butterfield DA. Free Radic Biol Med. 2013 Dec 16;67C:387-395. Germline Signaling Mediates the Synergistically Prolonged Longevity Produced by Double Mutations in daf-2 and rsks-1 in C. elegans. Chen D, Li PW, Goldstein BA, Cai W, Thomas EL, Chen F, Hubbard AE, Melov S, Kapahi P. Cell Rep. 2013 Dec 26;5(6):1600-10. Lysosomal NEU1 deficiency affects amyloid precursor protein levels and amyloid-[bedta] secretion via deregulated lysosomal exocytosis. Annunziata I, Patterson A, Helton D, Hu H, Moshiach S, Gomero E, Nixon R, d'Azzo A. Nat Commun. 2013;4:2734.

EFFECT OF NEURODEGERATION.
Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases including Parkinsons, Alzheimers, and Huntingtons occur as a result of neurodegenerative processes. As research progresses, many similarities appear which relate these diseases to one another on a sub-cellular level. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously. There are many parallels between different neurodegenerative disorders including atypical protein assemblies as well as induced cell death.[1][2] Neurodegeneration can be found in many different levels of neuronal circuitry ranging from molecular to systemic.

ALZHEIMER DISEASE. Alzheimer's disease is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus.[14] Alzheimer's disease has been hypothesized to be a protein misfolding disease (proteopathy), caused by accumulation of abnormally folded A-beta and tau proteins in the brain.[15] Plaques are made up of small peptides, 3943 amino acids in length, called beta-amyloid (also written as Abeta or A). Beta-amyloid is a fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that penetrates through the neuron's membrane. APP is critical to neuron growth, survival and post-injury repair.[16][17] In Alzheimer's disease, an unknown process causes APP to be divided into smaller fragments by enzymes through proteolysis.[18] One of these fragments gives rise to fibrils of beta-amyloid, which form clumps that deposit outside neurons in dense formations known as senile plaques.[19][20]
PARKISON DISEASE.

Parkinson's disease is the second most common neurodegenerative disorder and manifests as bradykinesia, rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. Parkinson's disease is a degenerative disorder of the central nervous system. It results from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain; the cause of cell-death is unknown. The following paragraph is an excerpt from the Pathophysiology section of the article Parkinson's disease. The mechanism by which the brain cells in Parkinson's are lost may consist of an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. The alpha-

synuclein-ubiquitin complex cannot be directed to the proteosome. This protein accumulation forms proteinaceous cytoplasmic inclusions called Lewy bodies. The latest research on pathogenesis of disease has shown that the death of dopaminergic neurons by alpha-synuclein is due to a defect in the machinery that transports proteins between two major cellular organelles the endoplasmic reticulum (ER) and the Golgi apparatus. Certain proteins like Rab1 may reverse this defect caused by alpha-synuclein in animal models.[21] Recent research suggests that impaired axonal transport of alpha-synuclein leads to its accumulation in the Lewy bodies. Experiments have revealed reduced transport rates of both wild-type and two familial Parkinson's disease-associated mutant alpha-synucleins through axons of cultured neurons.[10] Membrane damage by alpha-synuclein could be another Parkinson's disease mechanism.[7] The main known risk factor is age. Susceptibility genes including -synuclein, leucine rich repeat kinase 2 (LRRK-2), and glucocerebrosidase (GBA) have shown that genetic predisposition is another important causal factor. HUNTINGTON DISEASE. The following paragraph is an excerpt from the Mechanism section of the article Huntington's disease. HD causes astrogliosis[22] and loss of medium spiny neurons.[23][24] Areas of the brain are affected according to their structure and the types of neurons they contain, reducing in size as they cumulatively lose cells. The areas affected are mainly in the striatum, but also the frontal and temporal cortices.[25] The striatum's subthalamic nuclei send control signals to the globus pallidus, which initiates and modulates motion. The weaker signals from subthalamic nuclei thus cause reduced initiation and modulation of movement, resulting in the characteristic movements of the disorder.[26] Mutant Huntingtin is an aggregate-prone protein. During the cells' natural clearance process, these proteins are retrogradely transported to the cell body for destruction by lysosomes. It is a possibility that these mutant protein aggregates damage the retrograde transport of important cargoes such as BDNF by damaging molecular motors as well as microtubules.[10]
Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS/Lou Gehrigs Disease) is a disease in which motor neurons are selectively targeted for degeneration. In 1993, missense mutations in the gene encoding the antioxidant enzyme Cu/Zn superoxide dismutase 1 (SOD1) were discovered in subsets of patients with familial ALS. This discovery led researchers to focus on unlocking the mechanisms for SOD1-mediated diseases. Unfortunately, the pathogenic mechanism underlying SOD1 mutant toxicity has yet to be resolved. More recently, TDP-43 and FUS protein aggregates have been implicated in some cases of the disease, and a mutation in chromosome 9 (C9orf72) is thought to be the most common known cause of sporadic ALS.

Recent independent research by Nagai et al.[27] and Di Giorgio et al.[28] provide in vitro evidence that the primary cellular sites where SOD1 mutations act are located on astrocytes. Astrocytes then cause the toxic effects on the motor neurons. The specific mechanism of toxicity still needs to be investigated, but the findings are significant because they implicate cells other than neuron cells in neurodegeneration.[29]

Aging and neurodegeneration[edit]

The greatest risk factor for neurodegenerative diseases is aging. Mitochondrial DNA mutations as well as oxidative stress both contribute to aging.[9] Many of these diseases are late-onset, meaning there is some factor that changes as a person ages for each disease.[1] One constant factor is that in each disease, neurons gradually lose function as the disease progresses with age.

Therapeutics[edit]
The process of neurodegeneration is not well understood so the diseases that stem from it have, as yet, no cures. In the search for effective treatments (as opposed to palliative care), investigators employ animal models of disease to test potential therapeutic agents. Model organisms provide an inexpensive and relatively quick means to perform two main functions: target identification and target validation. Together, these help show the value of any specific therapeutic strategies and drugs when attempting to ameliorate disease severity. An example is the drug Dimebon (Medivation). This drug is in phase III clinical trials for use in Alzheimers disease, and also recently finished phase II clinical trials for use in Huntingtons disease.[4] In another experiment using a rat model of Alzheimer's disease, it was demonstrated that systemic administration of hypothalamic proline-rich peptide (PRP)-1 offers neuroprotective effects and can prevent neurodegeneration in hippocampus amyloid-beta 2535. This suggests that there could be therapeutic value to PRP-1.[30] Protein degradation offers therapeutic options both in preventing the synthesis and degradation of irregular proteins. There is also interest in upregulating autophagy to help clear protein aggregates implicated in neurodegeneration. Both of these options involve very complex pathways that we are only beginning to understand.[1] The goal of immunotherapy is to enhance aspects of the immune system. Both active and passive vaccinations have been proposed for Alzheimer's disease and other conditions, however more research must be done to prove safety and efficacy in humans.[31]