Fundamentals of Aging Has evolution become obsolete? What is aging? Aging is the gradual progressive decline of life essential functions eventually leading to death

How does it manifest itself? Telomere shortening (verses cancer) Advanced Glycosylation Endproducts (AGEs) Protein Crosslinking The mitochondria Reactive Oxygen Species (ROS) Recycling? (e.g. lysosomal storage disease) Immune senescence Decline of basal metabolic rate by 1% per year Deregulated nutrient sensing Loss of proteostasis Epigenetic alterations Genomic instability Altered cellular communication

Protein crosslinking – slow cooker?

Telomere integrity

T-Loops schematic

Fortunate procaryotes

Extending Telomeres

Natural Telomerase Activities

Lung Cancer Karyotype

Longevity versus Cancer (How can we maximize or chances to keep up with the never ending race against cancer for as long as possible?

Stem Cell exhaustion

Defining reserves Reserves are defined as the maximum difference between the maximally possible e.g. metabolic, physiologic and cognitive performance and the minimum performance required to deal with and properly respond to 99% of encountered situations and stressors

Declining reserves – When does pathology start Declining reserves – When does pathology start? Perfomance maximization instead of pathology?

Premature Aging (Progeria) (suicide clock)?

The evoluation of Aging How could aging enter our genome? When and why did aging evolve? No aging in RNA world What changed during the transition into the protein world? What are the benefits of aging? Aging was the only way to adjust genotypes to environmental changes

Why can’t we identify all anti-aging factors? Five hypothetical factors for long life, supported by the almost simultaneous failures Mutations in one essential life process set the stage for mutations in the remaining processes essential for life? supported by the almost simultaneous failures of multiple essential life processes How to determine all necessary anti-aging interventions?

How to select the best model organism? How to choose the best model organism depending on the scientific question? Example: The giant squid Too noisy data in current model organisms, i.e. yeast, worm, fly, fish and mice

What are the properties of the ideal model organism to decipher aging? Lifespan extension by the too small because true effects could easily be masked by noise The need for a model organism possessing a much higher sensitivity to lifespan to minimize the risk for lifespan regulating mechanism to be masked my noise The honeybee as the best solution

Why the honeybee? We need a model containing the answer rather than models in which we are still looking for the answer Worker bee = negative control, queen bee = positive experimental Removing only one single difference between queen and worker to generate a list of lifespan extending alterations.

Who are the drivers of Aging? Are changes in gene expression patterns actively driving the aging process (inbuilt suicide clock, e.g. salmon), developmental changes or are they only adaptations to accidental morphological changes resulting in the decline of the physiological, metabolic and cognitive reserve, e.g. induced by AGEs?

Lifespan checkpoints? Variations in the gene expression patterns of different lifespan intervals are much higher than variations in gene expression patterns of different genotypes for the same lifespan interval. Are their checkpoints in individual life cycles similar to the checkpoints in the cell cycle? Could optimal anti-aging interventions potentially depend on and change with particular lifespan intervals? Supported by the fact that the efficacy of drugs changes with age

Future Medical Interventions? Can there ever be a magic bullet for reversing aging for all? How can we best deal with the ever expanding, partially interdependent medical data? Who will determine the best medical treatment and on what bases? Is aging a disease? What should be the role of medical doctors in the future? What is healthy?

What is the future of drugs? Can mandatory genotyping yield in an unparalleled increasing of approved drugs? Do our current drug approval procedures need to be replaced by approving treatment procedures instead? Drug safety verses amount of available treatment options?

What can you do to survive? Patei fuer Gesundheitsforschung http://parteifuergesundheitsforschung.de/ SENS Foundation (http://www.sens.org/) Fighting Aging (https://www.fightaging.org/) Besiege den Tod (http://www.besiege-den-tod.de/) International Longevity Alliance (ILA) (http://longevityalliance.org/) Zoltan Istvan for American President (http://www.zoltanistvan.com/) Transhumanism (H+) Questions to Thomas Hahn at Thomas.F.Hahn3@gmail.com or cell phone at 0176 / 211 39 634 or via Skype at tfh002

Current Contact Information Office Phone (landline): +1 (501) 682 1440 Smart Phone: +1 (501) 303 6595 Flip Phone: +1 (318) 243 3940 Google Voice Phone: +1 (501) 301-4890 Skype ID: tfh002 Work Email: TFHahn@UALR.edu Private Email: Hahn5Thomas@gmail.com Twitter: @Thomas_F_Hahn Facebook: https://www.facebook.com/Thomas.F.Hahn LinkedIn: https://www.linkedin.com/in/thomas-hahn-042b2942/ ResearchGate: https://www.researchgate.net/profile/Thomas_Hahn10