The New Theory of Aging - A Degenerative Disease

imagine the following we live in a world where people routinely live to 150 years of age there's a strange family who for some reason at around 80 become very ill their skin and hair start to deteriorate their muscles begin to degrade and their bones start to lose density this is strangely abnormal and so a german scientist begins to study them and discovers a strange disease that causes the observed rapid deterioration in this family the disease is named after him and scientists begin working on ways to cure it what i've described is werner syndrome except of course the timeline has been doubled people normally live to around a 75 and people with werner syndrome not long past 40. i ask you this why does it seem odd for the people in our imaginary society to die at 80 and normal for people in our real society to die at the same age age is a disease the concept sounds wrong and will be scoffed at by many but until we normalize this idea we won't be able to adequately address it when i say age is a disease i'm not saying time or getting old is the disease i'm talking about the physical manifestations we associate with getting old twins with different lifestyles can have very different ages despite having lived the same amount of time like all diseases some people are more susceptible or resilient to it than others the difficulty in classifying aging as a disease is it isn't as tangible as other diseases and since it also occurs for every single person who lives it's even easier to say nah that's just how things are but humans have only recently in geological time been able to consistently live to such extreme ages it was never an evolutionary benefit to avoid aging when we look at apex predators like whales and sharks who have been able to live and reproduce in the same environment for hundreds of millions of years they don't really seem to age now there's a lot of difference between humans and sharks and it would be naive to use that as evidence but let's consider some past theories the oldest most common theme in the theory of aging is that our dna becomes damaged loses its information and thus cells lose their function and deteriorate over time we experience these hallmarks of aging and eventually our bodies fail to maintain itself loss of information as we'll soon learn is the cause of aging but it's not a loss of genetic information that causes this deterioration rather it's a loss of epigenetic information information stored in your dna is what we call digital this is information that is binary in nature either you have it or you don't if we look at this word we cannot be certain what it is the information is simply lost and if we don't have a backup or a copy it's lost forever information stored in your every genome is what we call analog information it exists physically and can exist in many different forms if we imagine the previous word from before was written in pencil in analog format and then erased we can observe the ever slight compressions left behind when it was written to reconstruct the information if aging was a loss of genetic information then that would be the end of it nothing we could do yet we now know that we don't lose any genetic information as we get older we can see this in clones which go to live normal and expected life spans and in 2012 shinya yamanaka won the nobel prize for showing that adult skin cells could be converted into pluripotent stem cells proving cells could be youthful again so if no genetic information is lost what causes aging imagine two rooms in one room you put a bunch of business majors and computers and in the other a bunch of culinary graduates and stoves over time this room becomes an office and this room becomes a kitchen now slowly but gradually you start putting business majors and computers into the kitchen and culinary students and stoves into the office after a while it's quite unclear which is the kitchen and which is the office workers in both rooms get into each other's way as they try to do their work the owner of the company who runs these rooms realizes that work efficiency has plummeted and it's no longer profitable to keep going at which point the two rooms are vacated and the business venture ends the workers and their respective instruments represent epigenetic factors in each cell over time the disease we call age causes the wrong epigenetic factors to build up within the cell this causes the cell to lose its identity and ability to function normally at which point it becomes senescent or marked for death if too many cells become senescent well let's just say it looks a lot like someone of old age but what evidence is there to support this it started with yeast a simple elegant unicellular fungi the average yeast cell can divide about 26 times before coming senescent or shutting down werner's syndrome as mentioned in the introduction causes rapid aging in organisms researchers mutated a gene in the yeast which would cause the onset of a werner's like syndrome and thus the consequences of it as yeast gets older its nucleolus fragments and the dna inside used for creating ribosomes leaks out this dna is self-replicating and thus creates multiple copies of itself in what are known as extra-chromosomal rdna circles when induced with werner's syndrome yeast rapidly accumulated ercs and died soon after now this creates two hypotheses either aging causes the creation of ercs or the ercs cause aging to test this researchers inserted multiple ercs alone into healthy yeast cells and observed the same thing rapid aging and deterioration so it seemed as if ercs caused aging but to solidify this hypothesis they needed to see what happens if the cell was able to remove them as mentioned before our dna is digital so losing information is a big deal as a result our cells are very good at protecting and repairing dna in yeast cells the rdna isn't supposed to be outside of the nucleolus and thus the cell tries to fix this problem within the genome this task of fixing the genome is principally carried out by proteins called sirtuins sartunes are found in all domains of life and are often referred to as longevity enzymes as they regulate the cell to maintain its genetic health and repair damaged dna sirtuins are also histone deacetylates what does that mean the epigenome is the reason a brain cell behaves differently from a heart cell despite containing the same genetic information this is mostly accomplished by physically controlling which genes are available to be read and which are off limits normally your dna is wound around protein complexes called histones when it's tightly wound around a histone the genetic information inside cannot be accessed thus genes within it are off limits however if we attach an acetyl group to the histones this reduces the interaction between them and the dna allowing it to unwind and relax a bit cells place acetyl groups on histones near relevant genes for their function so heart cells have acetylated histones near heart cell genes and brain cells have acetylated histones near brain cell genes stratums are deacetylates which means wherever they are the dna is wrapped up tight and whatever genes are near them are inaccessible if however the sirtuin leaves its original position to go help repair dna that gives the histones that were originally blocking genes the opportunity to become acetylated and relaxed this then gives the previously silenced genes an opportunity to transcribe themselves but we're getting a little ahead of ourselves we return to our original hypothesis that ercs and yeast cells cause aging if the yeast cell was able to remove the ercs it should therefore slow aging and live longer researchers inserted an extra sirtuin gene into the yeast genome meaning the creation of extra sirtuin proteins and sure enough not only did the ercs disappear but yeast cells with an extra sirtuin gene sequence lived 30 percent longer and this was interesting it would seem that a yeast cell's ability to quickly fix its dna correlated to longer and healthier lifespans now this does seem to mesh with the original theory of dna damage being the cause of aging but it still wouldn't explain how old dna can become youthful again and this is where our kitchen in office metaphor from before comes into play as sirtuins leave their original locations to help clean up dna damage and genomic instability proteins that shouldn't exist in our cell start to be created if the dna damage is significant and persistent sirtuins rarely have the opportunity to return to their original location and thus these genes that should have never existed accumulate and create epigenetic noise which eventually creates cell senescence this revelation has been proven in multiple controlled studies in multiple organisms introducing methods to control epigenetic noise and promote genetic stability increase lifespan and more importantly vitality during the organism's life sirtuins aren't the panacea of slowing or stopping aging and merely one of multiple enzymes that can be manipulated to do so all of which indicate two repeating trends in age-related research aging is the result of epigenetic noise causing a loss of cell identity and stabilizing and even reverting the epigenome to a younger state diminishes or even completely negates the effects of aging when aging is treated like a disease then it seems quite unnecessary in fact it seems possible to completely prevent aging as we know it dot dot [Music] you

Channel: But Why?

Views: 703,077

Keywords: age, aging, sirtuins, why do we age, old age, epigenetic, epigenome, epigenetic noise, david sinclair, sinclair

Id: qoc29xFMRdM

Length: 10min 35sec (635 seconds)

Published: Fri Dec 25 2020