Aging 9-15-2018 10 am CST Scientistmel.com Twitter.com/scientistmel Patreon.com/scientistmel 9-15-2018 10 am CST

Aging How do we get old? What causes aging? Can we slow the process? Can we reverse the process?

Aging DNA damage and changes Loss of protein function Reactive oxygen in cells Lack of stem cell division Decrease in effective cell communication

Aging The aging process still has some mystery to it, but science has worked to find some key roles that play into how we age. Much of it comes from DNA modifications and damage that goes unrepaired. As cells age, the ability to repair DNA is lessened which worsens the effects of aging. When the DNA in the cell becomes far too damaged to repair, the cell goes into what we call senescence aka getting old. Changes in important genes can cause aging to occur as organ and tissue functions are altered. Once the cell enters senescence, tissues start to shrink (atrophy) and inflammatory chemicals are released. This inflammation disrupts our innate immune system. This issue with inflammation can be particularly problematic to elderly people and a source of mortality for them. Elizabeth blackurn received the nobel prize in physiology and medicine for her work in genetic structures discovering telomerase…an enzyme linked to DNA protection. She was working under a theory called Hayflick’s limit. Hayflick found that mammal cells have a specific number of times that they can divide before they stop dividing and die. The more your cells have to divide the closer you are to death as well as aging. There is still some argument over Hayflick’s limit as multiple factors play a role in aging, but it was a springboard for the discovery of telomeres and telomerase.  

Aging Telomeres and Telomerase Protective DNA caps Telomerase <-enzyme replaces caps Loss of telomeres = loss of DNA As a side note…cancer cells are immortalized through a mutated version of telomerase consistently replacing these ends.

Aging Protein folding Essential for function Shape dictates function Misfolded proteins don’t work

Aging Proteins need to be folded a certain way for them to work. Scientists are not yet sure if protein folding is causing aging or if aging is causing the misfolding of protein. What happens when proteins are not folded correctly? They are not able to have biological compounds fit into their spaces properly to either build molecules or break down molecules. Much like taking a piece of paper and folding it into a cup formation…if you change the shape of the paper., it will no longer hold water. If proteins can’t effectively do their job, they can not break down biological molecules into important mini molecules for life or build important molecules for other necessary purposes.  

Aging Reactive Oxygen Species (ROS) Mitochondria produces ROS High amounts wreck cells Some is still needed.

Aging ROS causes cell damage The translates to tissues Tissue damage leads to organ damage Organ damage leads to system failure

Aging Stem cell Division decreases Needed for repair Susceptible to DNA damage

Aging Sdults carry stem cells that are used to repair tissues and organs. Stemcells lose their ability to divide with aging. No one really knows how this happens but the effects are a loss of ability for the body to repair itself. It is suspected that DNA damage is the culprit for stem cell changes.  

Aging Cell communication Breaks down with age Cells lose important signallers Cells increase too many signallers

Aging Cellular communication is important especially when it comes to healing as well as cellular maintenance. If cells can not effectively talk to one another, a steady loss of function can occur. Studies have shown that older mice when injected with younger mice blood have restored heart, brain, and skeletal function in these older mice. The younger mice have a better balance of GDF11 which is a growth factor for cells as well as NF-kb which is a transcription factor over expressed in the elderly…NF- kb is involved in making proteins through DNA transcription and cell survival.  

Aging Can we slow the process? Some evidence for calorie restriction Lowering visceral fat Lifestyle choices for reducing stress Lifestyle choices including exercise

Aging Recent studies involving human trials have shown that decreasing calorie intake by 15% for 2 years slowed aging and protected against age related diseases. This also reduces oxidative stress the ROS that wrecks cells…this ROS also has been linked to alzheimers and parkinonson’s disease. While reducing caloric intake is linked to slowing aging, it is important not to go too far and hurt yourself with starvation. Lifestyle choices also play a role…smoking is linked to increasing aging as it has a system wide effect. Visceral fat contains larger amount of biochemicals in cellular pathways that contribute to processes associated with aging. Nutrition is essential in slowing aging…as well as exercise to encourage muscle building as well as bone density.  

Aging Can we reverse it? In mice, yes. Changing genes Adding telomerase

Aging A ground breaking study at the Salk institute showed a reversal of cellular aging through human cells in mice. They were able to age the cells and then reverse the aging successfully by turning on certain genes that were able to revert adult cells back to an embryonic state. This study showed healing of injuries in mice as well as extending the life of mice by 30% who had Hutchinson’s disease. This reinforces the idea that epigenetic changes are largely responsible for the aging process. Mice had their telomerase replaced and aging reversed. This study showed that mice without telomerase could have their aging cells reversed once telomerase was introduced. There is some skepticism as this particular model does not really mirror telomerase activity in humans as they do have it and are not born without it. However, it is still useful data of which more research can progress. Of course more information is needed before we can start doing such things on humans…but this does give us a point to start working to treat age related injuries and illness.  

Aging How do we get old? What causes aging? Can we slow the process? Can we reverse the process?

https://embryo.asu.edu/pages/hayflick-limit https://www.the-scientist.com/the-nutshell/caloric-restriction-slows-signs-of-aging- in-humans-29911 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755412/ https://www.sciencedaily.com/releases/2018/03/180322141008.htm https://www.the-scientist.com/features/how-we-age-35872 https://www.nature.com/scitable/topicpage/aging-and-cell-division-14230076 https://www.scientificamerican.com/article/aging-is-reversible-at-least-in-human- cells-and-live-mice/ https://www.ncbi.nlm.nih.gov/pubmed/28538216 https://www.nature.com/news/2010/101128/full/news.2010.635.html https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1933587/ https://embryo.asu.edu/pages/hayflick-limit https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850851/ https://www.nia.nih.gov/about/living-long-well-21st-century-strategic-directions- research-aging/inflammation-plays  

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Aging 9-15-2018 10 am CST Scientistmel.com Twitter.com/scientistmel Patreon.com/scientistmel 9-15-2018 10 am CST