Death

Strong disclaimer: My knowledge on biology is very limited. What I write below is based on my understanding from reading the book and I may have misunderstood or misinterpreted some concepts. All mistakes are mine I learned lots of new things reading this book. Theory of antagonistic pleiotropy - Genes that are beneficial in early life can have detrimental effects in later life. Relationship between size, heart rate, lifespan to metabolic rate. Kleiber’s law states that metabolic rate scales to the 3/4 power of body mass. Natural limit of life span is roughly 120 years for humans. Genes: Units of information that contain information on not only how to reproduce an organism and pass on its traits but on how to build an entire organism from a single cell and keep it functioning. Genes reside in our DNA. The information around DNA and RNA in chapter 3 “Destroying the master controller” is fascinating. Proteins: Genes contain information on how to make protein. These are the workhorses of the cell. They regulate flow of molecules in and out of cells, catalyze chemical reactions, provide structure to cells and tissues, and perform many other functions. Our nervous system depends on proteins to transmit nerve signals and store memories. Antibodies are made of proteins. Ribosomes carry out complex process of reading mRAN to synthesize proteins. There are mistakes in this process too. Sometimes mRNA contains mistakes or sometimes ribosomes misreads it. Protein folding: Proteins are made up of long chains of amino acids. These chains fold into specific three-dimensional shapes that determine their function. Misfolded proteins can lead to diseases such as Alzheimer’s and Parkinson’s. DNA evolved from RNA as a way to store genetic information stably. Thousands of changes are inflicted on DNA in each of our cells every single day. Cell division is like copying a text three billion long where an error occurs sometimes there’s mistake in copying when cell divides. There is repair mechanism in the body to fix damage to DNA. I found this mind boggling. Cells have limit on how many times they can divide. This is called Hayflick limit. Cancer cells are exception to this limit. I don’t understand how cells stop dividing. Why do chromosomes shorten with each division and role of telomeres. Recycling the cell’s garbage - The process by which cells are destroyed and recycled. As we age, this machinery becomes less effective. Proteins that are incorrectly made or misfolded need to be indentified. Cells have a complex machinery to detect the buildup of these proteins and destroy them. Autophagy is used to ensure cells develop normally and get rid of defective proteins or aging structures. This is detailed in chapter 5 “Recycling the garbage”. Alzheimer’s is caused by cell’s inability to manage excess of unfolded proteins. This in turn is caused by damage to control systems that manage quality control and recycling machinery of the cell. The damage to this machinery is caused by aging. A stupid question: Why can’t we create an artificial garbage disposal system to clear these misfolded proteins? Caloric restriction (CR) - Reducing calorie intake without malnutrition has been shown to extend lifespan in various organisms. This is discussed in chapter 7 “Less is more”. This chapter introduces TOR and how it’s connected to CR and how inhibiting TOR can enhance health. TOR is helpful in early life for growth but it is unable to switch itself off when growth becomes excessive leading to cell deterioration and aging-related diseases. Chapter 8 discusses the IGF-1 pathway and NAD and their role in aging. IGF-1 pathway and TOR pathway are connected in complex way. Inhibiting IGF-1 pathway has been shown to extend lifespan in various organisms. Metaformin, a diabetes treatment drug is thought to work by inhibiting IGF-1 pathway. How this drug works in not entirely clear. NAD is a molecule that is involved in energy metabolism and DNA repair. NAD levels decline with age, and boosting NAD levels has been shown to improve health and extend lifespan in various organisms. Mitochondria: Gaia hypothesis. The powerhouse of the cell. I like the parallels drawn between how electricity is produced and exchanged in modern world through different ways. Mitochondria works similarly where it takes versatile forms of energy and converts them into universal energy currency of the cell, ATP. When cells need energy, it breaks the ATP bonds and use the energy released for any particular process in the cell. Mitochondria have their own DNA and can replicate independently of the cell. Mitochondrial dysfunction is thought to contribute to aging and age-related diseases. When we digest the food, especially carbohydrates, we are effectively burning the sugar that we obtain by breaking down the carbohydrates … Sugar combines with oxygen and releases carbon dioxide and water and releases energy in the process. That is exactly what we do when we breathe in and out. The energy released during respiration is used by the mitochondria to produce ATP. We inherit our mitochondria exclusively from our mothers… diseases due to defects in the mitochondrial genome are inherited entirely from the mother. As we age our mitochondria still work but they have accumulated the defects. Not only do they produce energy less effectively, but they have becomes creakier and less effective at their myriad other tasks. ...