Why Do We Age?

Did you know that there are certain species on the face of the Earth that are truly and literally immortal? Yep. They never die. Of old age, that is. I am not talking about some microscopic bacterial life or stubborn viruses in existence. No. Real animals. Take these two: turtles and lobsters. They literally don't age. When it comes to first one, I can't resist not quoting article in below refs* I read online—to the logical suspicion of endless turtle lifespan and why in the aftermath they don't crawl everywhere we look today, they answer, "Of course they die; otherwise we'd be swimming in turtles, but the weird thing is, they never seem to die of old age. It's always a disease, or a falling boulder, or Master Shredder". And this is a real truth, actually, including 'Master Shredder', who might be just a metaphor for us killing turtles for food or purses and belts or whatever we do with dead turtles. Joking aside, the very research of big turtles shows no evidence that their bodies change or mature after they pass their teenage years. They are literally capable of sexual reproduction until the end of time. And again, the glimpse from the noted article stating the obvious: "They can breed and lay eggs until the day they drop dead, and that means that, technically, a turtle can live and have sex forever". The same is with lobsters—well, I am not sure about the sex thing, but they don't age either. Just grow bigger and bigger and bigger until they finish their lifespan in the kitchen of some fancy restaurant. When they got so big that their shell couldn't sustain them anymore, they just got out and started growing a new one. I am sure somewhere out there in the bottom of some sea or ocean there are lobsters today old enough that they are actually living witnesses of Darwin's "Beagle" sailing out for her historical voyage around the world in the early nineteenth century.

I am sure by now you already started growing an ultimate regret about why on Earth you weren't born on one of the Galápagos Islands, hatched out from some egg, and spent eternity practicing martial arts—and instead ended up being a human. But seriously, the title's question is real and open for scientific discussion. And for theatrical purposes, let me repeat it: "Why do we age?" And ultimately die? Surely, if we find out why, the next question is, of course, can we cheat it? Expand it? Live forever? If we find out that is possible, the third question in the row imposes. Should we do it?

But, before we dive into deeper thoughts and evaluate leading theories and hypotheses, I remember when I started with a blog, one of my early small posts in the humor thread was a couple of famous quotes about life itself. As far as I remember, many of them were really plain and intelligent jokes, but the one said by Ronnie D. Laing, a Scottish scholar who dedicated his life to research of mental illness and psychosis, was probably hitting the target in the bullseye. He said, "Life is a sexually transmitted disease, and the mortality rate is one hundred percent." If we extract the humor from this one-liner, what we really get is, perhaps, the ultimate truth. Reaching your or my old age, or death itself, might be nothing else than a genetic disease, in a stretched form of the definition of the word 'disease', and we might be able to do something about it.

Well, contrary to lobsters and turtles (and some other 'immortal' species like certain types of whales, seashells, sponges, hydras, etc.), we are mammals, pretty different kinds of anim... ahem, species. We are different in many ways, genetically speaking, and compared to, for example, reptiles, we cannot regrow our teeth or entire body parts as well, and our DNA, as it seems, has limited regeneration ability that fades with years and ultimately gets exhausted the moment before death. For those lucky to die of old age.

Two leading theories have been posted until today. First, it was proposed that living organisms have some sort of genetic expiration time, written in DNA. In other words, we are all combinations of genes of our parents and their parents and parents before them, all the way back in the history of our families, and this lucky mixture of genes, written in all of our cells, is built to last only a limited period of time. Even though this theory seems so unbelievable and far-fetched, it is actually hinted at in labs. In some genetic research of worms, altering their genome and some specific genes 'produced' the worms who actually lived four times longer than their unaffected peers.

If those genes with encoded expiration dates really exist, finding and rewriting them might be able to increase our lifespans. However, the second theory is much more appealing and easier to understand. It simply says that our cells die at the end of the cycle due to too much damage they suffer over time. To simplify it, there are two types of DNA in our cells: nucleus DNA, which defines us, located in the cores of cells, and mtDNA, residing outside the nucleus and in special parts of the cells called mitochondria. While nucleus code is used during the cell's division to produce another cell with the same DNA, mtDNA is there mainly to produce energy for the cells from the food we consume. And both DNAs can be damaged over time due to various factors, and as time passes over years and decades, the damages become more severe, and at the end of the process, which we know as aging, the entire organism dies. If we focus on mtDNA first, it's logical that these 'power plants' of our cells endure way more pressure than their fellow DNA in the nucleus, as they are in the first front lines hit by influences of the food we eat. From that food they produce energy and, in the process, a very bad byproduct called ROS, 'Reactive Oxygen Species', which are a variety of oxygen-based molecules that are very dangerous for the power plant itself and very capable of ultimately damaging the cell and mtDNA to the point of full destruction in the process of unwanted mutations. Basically, if you are now thinking that a special sort of diet or simply eating less food would give you a longer life, think again. In fact, if you do so, it is logical that more DNA in mitochondria will survive over time in their intact form, but on the other side, restricted diets in lab animals show that they grow slower than normal, reproduce less than normal, and have more endangered immune systems than usual. We need food. It is essential. So, don't stop eating, but try to do it properly and in the most healthy way possible. But the theory of lifespan directly related to the healthy mtDNA is proven in poor lab mice in which scientists encoded a faster genetic mutation of mitochondrial DNA, which resulted in faster aging and a shorter lifespan—they actually lived three times shorter than their 'normal' friends and cousins. So oxygen is bad and ultimately kills you. And yet we cannot live without breathing, can we? A paradox of creation, especially if you are a believer.

What about nucleus DNA in our cells? Are they also causing aging in the process of mutation? Yes, due to mutation of the nucleus, DNA cells end up in a cancerous or non-cancerous state, which is pretty much a defect and the cell's death. During an organism's growth, cells divide in the process called 'mitosis'—one 'cell, by using code in the nucleus, DNA, divides into two new cells, which are exact replicas of the parent cell. Even after an organism has fully matured into its adult stage, cells still continue to divide for the purposes of reproduction and replacement of lost or dead cells. However, as it seems, both resulting cells are not really and exactly the same as their predecessor cells. Yes, the code in chromosomes is the same, but the ending caps of the chromosome structure are getting shorter after each division. These caps are called 'telomeres', and their main purpose is to protect the end of the chromosome from connection with other chromosomes. After numerous divisions of the cells, telomeres run out, and this is pretty much the end of it. The cells are after that doomed. But this is not the end of all the ways of the one-cell doomsday scenario. According to Aubrey de Grey, one of the leading scientists in biogerontology, the scientific subfield of gerontology concerned with the biological aging process, over the years the cells accumulate various molecules that are no longer useful and potentially harmful. And not just within the cells, but also in the space outside cells. Those molecules are scientifically called 'intracellular and extracellular aggregates', but their real names are 'junk molecules', and, like the name suggests, the more of an accumulation of junk, the more dysfunctional the organism becomes. Dr. Aubrey de Grey proposed even more processes, on the cell level, influential in aging, and thanks to his research and the entire scientific mainstream, which is still ongoing research, we definitely understand it more than ever.

Benjamin Franklin once said that in this world nothing can be said to be certain except for death and taxes. I, for one, would definitely like to see the end of death and taxes for sure, and even though it is very hard to imagine a world without taxes, death, after all, might be a very different story. Well, understanding aging is one thing, and finding the cure for it is surely another, not to mention manufacturing a 'cheating-death' pill is not really in the realm of possibility anytime soon. Even the 'genetic pill' that will be able to slow down aging or the one capable of reverse engineering that would replace the mythical fountain of youth (or Lazarus Pit from the DC Comics franchise) is far away from the horizon. However, what is on the horizon and even much closer is the effort and research. Last year Google announced a plan to invest lots of money into California Life Company, aka Calico, and if you go to their website, the first thing you will see is their motto, "We're tackling aging, one of life's greatest mysteries." If you dive into the current stage of IT-leading entrepreneurs and futurists, it seems they all are sharing the same enthusiasm in the "curing death" realm, and I can't help but state the similarity with A.G. Riddle's new novel called "Departure", which pretty much influenced me to write this post, even though I was planning it for a while. I will not spoil the reading for you, but in a nutshell, one of the background stories in it is dealing with immortality, which, in one way or another, resulted in the end of civilization as we know it. I am encouraging you to read the book; it is definitely one of the best novels of the year in the sci-fi realm. In short, in the aftermath related to immortality, one of the leading characters from the novel, Sabrina Schröder, was portrayed giving a TED talk about cheating death and why we should avoid it on a large scale. That's all I would say. Sorry, but you would have to read the entire book to understand everything. I will just say that I hope Riddle's 'Titans' are not predictions for 'Googlers' or 'Applers' or 'Calicos' or whatever the name they come up with in the upcoming breakthroughs in aging research.

As for me, I am sure I wouldn't mind prolonging life a bit, or a little bit, or a 'frakking' long bit, but avoiding death is raising lots of other dilemmas in morality and everything else. It could be handy on long interstellar voyages, though, but it is not far from the truth that reproduction and further evolution of humans would be in real danger if everybody took the immortality pill and if we were stuck in the current stage of evolution without offspring of any kind. Morality issues of a potential cloning of a human being and making it immortal might not be too different.

Extending the lifespan is a very different story. I would always take the red pill and jump into the rabbit hole without hesitation. Life is way too short. After all, lifespan is something nature and evolution have been working on for centuries. If we learn to push and help a little with science, I would definitely be aboard.

Refs:
http://www.calicolabs.com/
http://www.medicaldaily.com/cure-aging-google-plunks
http://www.telegraph.co.uk/.../trying-to-cure-ageing.html
https://en.wikipedia.org/wiki/R._D._Laing
http://genetics.thetech.org/original_news/news10
http://www.todayifoundout.com/index.php/2014/05/age/
http://www.agriddle.com/departure/sabrina
http://www.agriddle.com/Departure
* http://www.cracked.com/animals-that-are-immortal.html
http://www.aboutdarwin.com/voyage/voyage03.html

Image credits:
http://nocamels.com/2013/12/stop-aging-to-prevent-alzheimers/
http://nocamels.com/2015/06/genetic-sequencing-evolution-cancer-brca1/

Genetic Genealogy

Recently, my five-year-old boy asked me the question I knew it would eventually come. The very question all parents are inevitably faced with when the right time comes. With my son it came in the simplest form: "What is God?" popped occasionally after tons of OMGs he heard everywhere in his realm of cartoons, video games, YouTube channels, and TV shows. I wasn't prepared completely. I mean, I had a pretty good idea of how to explain mythical phenomena, unknown and unexplainable tales, and the very concept of belief, but I didn't know how to do it without destroying Santa Claus, the Easter Bunny, and other fairy tales he enjoys every year. To me, it's much too early for that age in life. It would only add disappointment and confusion, and it's better to leave it for a little later. So I performed good old evasive maneuvers, and in a couple of curves, I succeeded in changing the topic and postponing the inevitable for the next time, which will come probably sooner than I think. The truth is, while it is not too difficult to explain the absence of God with the simple Occam's razor principle, it is extremely hard to comprehend why so many people live in their world of prayers, worshiping the divine and believing in a wide variety of religious stories.

Gene -> DNA -> Chromosome -> Cell*

To be honest, whether or not God(s) is responsible for the very creation of life as we know it or it came after a long period of evolutionary 'tries and errors', one thing is for sure. Whoever the creator is, today we know a great deal about how the life laboratory works and almost completely understand the very basics of how one living entity grows from the stage of being a small seed (or two of them, to be precise, for many species) to a fully formed individual. It's all written in the biggest molecule out there, located in every single living cell. No matter if you are a virus, small bacteria, tree, ugly fly, or any kind of mammal, how you will look and what your capacity to dazzle will be are all written in the genes of your DNA molecule. To put it simply, one gene, or a group of them, is responsible for one property of you. They are virtually responsible for the way you are smiling, how you walk, why your hair is curly and blonde, how intelligent you are, how tall you are, why you love romantic movies and hate science fiction... They even define you to be either religious or skeptic, explorer or indigenous, emotional or psychopath... Basically everything that defines a personality. You can't escape from what you are, as it is simply carved in the stone and irretrievably combined in your DNA sequence.

But how does it really work? You probably heard that human genetics are only a couple of percent different from, for example, the genetics of chimps, while the Neanderthals differ by less than one percent. In human genetics, one parent is providing 23 chromosomes that are paired with the other parent's and stored in our cells in a total of 46. Chromosome sequencing counted a sum of 32,185 genes responsible for the unique appearance of each person. There are no two identical individuals; even identical twins differ on a genetic level, providing, for example, different fingerprints among hundreds of other genetic differences they have due to mutations in genes in their early development.

Map of Human Migration**

Contrary to all those differences between individuals, genetic genealogy, on the other hand, deals with similarities and identical sequences in the human genome, trying to classify humans in their groups of origin. This scientific effort is providing a better understanding of human migrations from the point when everything started for all of us back then in Africa. Many genealogy surveys are performing DNA testing for this purpose, and after less than a decade of mass analyses of DNA material and thousands of specimens, dozens of haplogroups (geographic areas or migrational paths occupied by people with the same or similar sequences in particular genes) are identified. The evolution of humans depends on one single thing—mutations in genes or errors made in the human genome due to environmental and other factors in the long history of human migrations. Homo sapiens lived entirely in Africa 150,000 years ago and started migrating out approximately 70,000 years ago. This process is considered finished only 2,000 years ago, when the last habitable island in the Pacific was occupied. Along the way our ancestors changed according to the conditions of the area they encountered and, evolutionarily speaking, divided into different races and groups. The research so far has given us very interesting results. Probably the most valuable fact given is that we all share the same family lineage. So far, among all tested DNA samples, it is not yet identified a sample with different rooted ancestors, both male and female. This hints that all people on Earth are having the same ancestors, scientific Adam and Eve, or, to be precise, 'Y-chromosomal' Adam and 'Mitochondrial' Eve.

In other words, everyone is related, and basically, if we had the data of all people who ever lived in the world,we could be able to create one giant family tree starting with the mentioned Adam and Eve. Even though they didn't know each other and lived separately by maybe 100,000 years, those two lineages are now the only ones that have survived in time. At least until we find different data in Y-DNA and mtDNA tests and find more ancestor roots. Only to be fair, after all the testing so far, it seems that even if we find any, they would only represent the side paths and small groups of humans sharing this hypothetical lineage(s). But how exactly is it possible to trace down your ancestors by analyzing the DNA code? The goal is to identify sequences in DNA that are in a way "immune" to mutations and passed from generations to generations almost unchangeable over time. There are sequences like that in the male sex Y chromosome passed only by the father's line. More than 100 sequences and their repetitions within the chromosome have been identified over the years and are today used in searching for a match for the most recent common ancestor when two samples are compared. Those sequences in the laboratory are called markers, and the more markers are used for comparison, the more precise the result could be, meaning you would be able to find a more recent common ancestor. The same is true with the maternal lineage test; only in this case, the X chromosome is useless due to severe changes over time, and instead mitochondrial DNA (mtDNA) is used, as this is passed by female ancestors in almost unchanged form. Similar to the Y-DNA test, markers are compared, only with a difference that this time it is not the number of repetitions of sequences that are being searched for but instead predicted changes or rare mutations in DNA recombination happening over time. The same procedure can be used for testing Y-DNA as well. The combination of these two testing types and comparing the results with the sample database provide matches in both recent and ancient ancestries and predict the appropriate haplogroup for the specimen along with the list of many relatives who already tested and were found in the database.

Haplogroup I (Y-DNA) distribution

You probably noticed that I am not trying to include too much scientific data and terms. If you are eager to dive deeper into this extremely interesting research, please find links and follow-up stories I included at the end of the post. Furthermore, I am not an expert in this field, just another reader following the research for more exciting discoveries and possible breakthroughs, and not only in genetic genealogy but in general DNA sequencing as well. With the courtesy of Beth Perry Steger, my dear Facebook friend, I own an NG's Genographic testing kit, the project with probably the biggest database of tested users, counting more than half a million users. Unfortunately, due to Serbian law policy that forbids sending any kind of biological samples via any kind of mail services, I am still waiting for the opportunity to do this abroad, but nevertheless, there are only a couple of haplogroups I can belong to, and the biggest probability is the haplogroup I (M170), where almost one-third of the population of Serbs are predicted to originate from. However, there are a couple more candidates for this region of the world if we exclude possible surprises and unknown data that happened in the history of my family. Long ago I started to fill out our family tree online and only have partial data for generations 5 and above, which is too small a data specimen to conclude anything valuable. I am sure I will know more in the following years and that this post thread dedicated to genetics will get its successor.

Finally, and probably completely unrelated to the genealogy described in this post, which is more of an anthropological study and not used for medical purposes, it would be unfair, to say the least, not to mention the large percent of noncoding DNA, or "junk DNA", portion of the human genome. More than 50% of the double helix is still not fully understood. It is determined that this part of DNA is not encoding protein sequences like those genes we mentioned earlier. It seems that a big part of these DNA sequences don't have any known biological function, and only recently some new theories and studies indicate that they are very active and serve in the regulation or fine-tuning of proteins. Differences in protein regulations and molecules might be responsible for different reactions of people to the same disease. It is not clear why, for example, identical twins react differently to some infections or diseases, to the extent that in the same environments, one twin can be more immune to the same disease compared to his sibling.

Anyway, entire DNA research is still young science, and I am sure more and more discoveries are still awaiting us in the near future. To make sure we better understand what our scientists are dealing with, just try to comprehend the size of this molecule. I found the fact that one single gram of DNA can hold 700 terabytes of data while one state-of-the-art personal notebook today contains less than one terabyte of internal memory. Imagine what can be stored inside. If even a tiny portion of junk DNA is really junk, we might learn how to use it to store files inside. One day instead of magnetic hard drives, you might have a personal computer that connects to cockroaches carrying your personal data.

Guide to Finding the Best DNA Ancestry Test
https://www.innerbody.com/dna-testing/best-dna-ancestry-test

* Cell division
http://www.bbc.co.uk/schools/gcsebitesize/science/

Image follow-up stories
** https://genographic.nationalgeographic.com/human-journey/
** http://en.wikipedia.org/wiki/Haplogroup_I2_(Y-DNA)#I-L69.2
*** http://en.wikipedia.org/wiki/Haplogroup_I-M170

Refs:
https://honestproductreviews.com/best-dna-test-for-ancestry/
http://www.familytreedna.com/faq/
http://www.familytreedna.com/snps-r-us.aspx
https://genographic.nationalgeographic.com/

Wiki
http://en.wikipedia.org/wiki/DNA
http://en.wikipedia.org/wiki/Geneology
http://en.wikipedia.org/wiki/Genealogical_DNA_test
http://en.wikipedia.org/wiki/Genetic_studies_on_Serbs
http://en.wikipedia.org/wiki/Haplogroup_I2_(Y-DNA)