Aging is not a process of decline; it is a process of continuing to meet life's challenges and of growing into a complete human being. Aging is a complex interaction of genetics, chemistry, biology and physiology; topics that are worthwhile to address. This book offers a good introduction to the biology and chemistry of aging. It emphasizes on cellular aging, and covers different areas and theories which deal with mechanism of aging. If the reader has some background in biology, then this is an excellent introductionary book to the biology and chemistry of aging. The book includes information on aging of cell and reversal of aging, DNA damage theory of aging, acidity, oxidative stress, radicals, insulin/IGF hormones, anabolic and catabolic hormones, testosterone and estrogen, energy through conversion between NAD+ and NADH, DNA transcription to RNA, and RNA translation to protein. This book is the first of its kind in providing scientists, physicians, pharmacists, engineers, teachers, computer programmers, and anyone with a background or strong interest in biology, chemistry, and aging. The book deals with scientific causes of aging, and philosophical and sociological implication of life-extension and research on aging. I recommend it for those serious about the biology and chemistry of aging.

Biochemistry of Aging

Wellness and LongevityBy Amin Elsersawi

AuthorHouse

Copyright © 2010 Amin Elsersawi
All right reserved.
ISBN: 978-1-4490-7380-0

Contents

Introduction..........................................................................................10Preface...............................................................................................12Chapter 1 Biology....................................................................................13Introduction..........................................................................................131-1 Cell Biology......................................................................................131-2 Cellular respiration..............................................................................301-3 Molecular biology.................................................................................381-4 Enzymes and enzymes mechanism.....................................................................471-5 Nucleophilic bond.................................................................................491-6 Bioenergetics.....................................................................................501-7 Cell Divisions....................................................................................521-8 Heredity..........................................................................................561-9 Immunology........................................................................................631-10 Human respiratory system.........................................................................861-11 Hormones.........................................................................................891-12 Microbiology.....................................................................................971-13 Food safety......................................................................................1021-14 Biomedical engineering...........................................................................1021-15 Psychology and clinical psychology...............................................................1031-16 Physiology.......................................................................................1081-17 Pharmacology and toxicology......................................................................1091-18 Human brain......................................................................................113Chapter 2 Chemistry..................................................................................1222-1 Atoms.............................................................................................1222-2 Molecules.........................................................................................1232-3 Bonding of atoms..................................................................................1252-4 Valence-Shell Electron-Pair Repulsion Theory (VSEPR)..............................................1262-5 Lewis structure of atoms..........................................................................1282-6 Lewis structure forions...........................................................................1282-7 Components of the cellular life...................................................................1312-8 Esters............................................................................................1472-9 Lipoproteins......................................................................................1522-10 Glycolipids......................................................................................1532-11 Sphingolipids....................................................................................1542-12 Steroids.........................................................................................1552-13 Mucin............................................................................................1562-14 Oxidation and reduction..........................................................................1572-15 Isotopes.........................................................................................1662-16 Polyatomic ions..................................................................................1732-17 Acids and basis..................................................................................1802-18 Acetylene series.................................................................................1862-19 IUPAC (International Union of Pure and applied Chemistry) Nomenclature...........................1972-20 Atomic Orbitals..................................................................................2112-21 Solubility.......................................................................................2142-21-1 Solubility Rules...............................................................................216Chapter 3 Aging.......................................................................................218Introduction..........................................................................................2183-1 Ketoacidosis......................................................................................2183-2 Oxidative stress..................................................................................2203-3 Super Dismutases (SOD)............................................................................2203-4 Anabolic hormones.................................................................................2233-5 the Free radical theory of aging..................................................................2493-6 Theories of Aging.................................................................................2553-7 [NAD.sup.+] and NADH in aging.....................................................................2583-8 Telomere and telomerase and life span.............................................................2613-9 Aging of cells....................................................................................2633-10 Senescence and titrating nuclear factors.........................................................2653-11 Ras Protein......................................................................................2693-12 DNA damage theory of aging.......................................................................2723-13 WRN Gene and Warner's Syndrom....................................................................2763-14 Late-Life mortality deceleration.................................................................2783-15 Reliability theory and redundancy exhaustion.....................................................2803-16 Fisher's reproductive value......................................................................2823-17 Basal Metabolic Rate.............................................................................2853-18 Sugar, fat and protein...........................................................................2883-19 BMR and aging....................................................................................2913-20 Heat shock and osmotic stress....................................................................2923-21 Gene therapy.....................................................................................2943-22 Polymorphism genetic and aging...................................................................3003-23 Accelerated aging diseases.......................................................................3023-24 Mitohormesis (Mitochondrial Hormesis)............................................................3073-25 Metabolic hormones affecting aging...............................................................3093-26 Polyphenol anti-aging............................................................................3113-27 Epigenetic inheritance and aging.................................................................3123-28 Methylation of DNA...............................................................................3133-29 Facts about aging................................................................................3193-30 Argument about aging.............................................................................3203-31 Authors' Exclusive Opinion about Causes of aging and Elongation of Life span.....................325

Chapter One

BIOLOGY

Introduction

Biology is the study of life. Biology is such a broad field, covering the structure, function, growth, origin and how they interact with each other and the environment that they live in. It is the branch of knowledge which treats living matters as distinct from non-living matters. Biology can be divided into groups:

Botany - the study of plants

Zoology - the study of animals

Microbiology - the study of microorganism

Biochemistry - the study of chemistry of life.

All above groups are further divided into subgroups:

Molecular biology - the study of interactions of biological molecules

Cellular biology - the study of the basic block of life

Physiological biology - the study of physical and chemical interactions of cells

Ecology-the study of the interaction of organs and the environment

The foundation of biology starts with understanding cellular biology which mainly covers seven topics as shown in the diagram below:

The cell is the fundamental of life, and all living things are composed of one or more cells. Cell theory provided a new perspective on the fundamental basis of life. Cells are subjected to mutations and development based on five principles; cell theory, evolution, gene theory, homeostasis, and energy.

The study of molecular biology also includes microscopic anatomy (histology) which can be examined by the aid of microscopes, dissection and inspection of dead bodies (cadavers). Human anatomy, biochemistry, and physiology are subjects of important discussion within biology. Anatomy involves several subjects such as: embryology, osteology, syndesmology, myology, angiology, the arteries, the veins, the lymphatic system, neurology, the organs of the senses and the common integument, splanchnology, surface anatomy and surface marking.

Medical doctors, especially surgeons and histopathologists and radiologists should have a thorough working knowledge of anatomy.

1-1 Cell biology

Cell age is dependent on the number of divisions a cell has undergone, not its chronological age. Cells typically go into senescence after about 50 divisions (Hayflick's limit), and are eventually removed by apoptosis. But most cells do not reach Hayflick's limit.

The cell is the smallest structural and functional unit of all living organisms. It is often called the building block of life. Some organisms are unicellular such as ameba and bacteria, and some are multicellular such as humans. Humans have about 100 thousand billions of cells with a diameter of about 10 micrometers and of a weight of 1 nanogram, Figure (1).

The Cytoplasm needs energy that is taken from glucose. Glucose and fructose have a similar number of carbon, hydrogen, and oxygen. Both have the formula [C.sub.6][H.sub.12][O.sub.6]. The difference is that glucose is hexagonal and has only one double bonded oxygen, and fructose is pentagonal and has two double bond of oxygen. Both are isomers and interchangeable under the process of photosynthesis. In addition to the carbohydrates, lipids, and proteins, the cell needs something called nucleic acid. Carbohydrates have a unique formula which is the ratio between carbon, hydrogen, and oxygen which is about 1:2:1. Lipids, protein, and nucleic acids have different ratios. We discussed carbohydrates, lipids, and proteins in full details in chapter 1.

Nucleic acid is used by the cell to store and use hereditary information. Nucleic acids known as nucleotides consist of three main components: a nitrogenous group, a phosphate group, and a sugar:

There are two types of nucleotides distinguished by their sugar: Deoxyribonucleic acid (DNA), which has one less oxygen than the other type ribonucleic acid (RNA). The function of DNA molecules is to store genetic information for the cell. RNA molecules carry genetic messages from the DNA in the nucleus to the cytoplasm for use in protein synthesis and other processes. We shall discuss nucleic acids in detail in the coming sections.

1-1-1 Membranes

There are several membranes associated with the cell. There are, for example, membranes to protect the cell from outside environment, membranes to insulate nerve fibers (which are called myelin), plasma membranes, and mitochondrial membranes. All membranes contain lipids and proteins with different ratios. Plasma has a lipid over protein ratio of 43.53/44.49, and the mitochondrial membrane of 24/76. As mentioned before in chapter 1 lipid has a hydrophilic head (loves water), and a tail which is hydrophobic (hated water), Figure (2).

Transmebrane proteins may be embedded in the lipid bilayers, on the edges of the membrane inside the cytoplasm or on the exterior face of the membrane.

In addition to the normal lipid (saturated lipid) there is an important type of lipid in the membrane is called the phospholipids in addition to the normal lipid (saturated lipid). These phospholipids have a polar head group and two hydrocarbon tails; one tail is saturated and the second is unsaturated because two carbons are double bonded as shown in Figure (3).

In Figure (3), one can see a kink in the double bond chain which prevents the bilayer tight packing and also makes the bilayer difficult to freeze. The effect of the kink and the floating of the polar head of the phospholipids make it fluid characteristics. It means that at low temperature, the membrane is in a gel state and slightly compressed. At higher body temperature the inside of the membrane is in a fluid state which allows the lipid molecules to move around, rotate, and exchange places. This allows movement of other components of the membrane, http://www.cytochemistry.net/Cell-biology/membrane_intro.htm.

Surrounding each of our cells is a membrane called the plasma membrane. The plasma membrane is a continuous double-layer of phospholipids, interweaved with cholesterol and proteins. Membranes have also cholesterol of different type of lipid. Different ratios between cholesterol and phospholipid molecules are in different membranes. The ratio in plasma membranes is 1:1. In cell membranes cholesterol can make up nearly half of the cell membrane. In bacteria the ration is 0:1 (bacteria have no cholesterol). Cholesterol is also present in membranes of organelles inside the cells, although it usually makes up a smaller proportion of the membrane. For example, the mitochondrion, the so-called "power-house" of the cell, contains only three percent cholesterol by mass. The endoplasmic reticulum (ER), Figure (4), which is involved in making and modifying proteins, is six percent cholesterol by mass. Since cholesterol molecule is smaller and weighs less than other molecules in the cell membrane, it makes up a lesser proportion of the cell membranes mass (roughly 20 percent). http://www.cholesterol-and-health.com/Cholesterol-Cell-Membrane.html.

Cholesterol consists of four hydrocarbon rings, which are strongly hydrophobic, and a hydroxyl (OH) group which is attached to one end of the cholesterol chain. Hydroxyl is known to be hydrophilic, meaning that cholesterol is amphiphatic. Cells produce cholesterol or draw it from extracellular sources with lipoprotein when it is needed, as cholesterol is continuously lost to the outside processes. The endoplasmic reticulum synthesizes the cholesterol which then binds to cellular proteins called caveolins in a 1:1 ratio. Both are involved in transport of de novo-synthesized cholesterol from the ER to the plasma membrane. Cellular homeostasis of cholesterol involves in the regulation of its amount and its movement between membranes. Cholesterol is therefore an important compound that affects the properties and functions of membrane proteins such as enzymes, receptors, or ionizing molecules for transportations and communications. Thus cholesterol helps maintain the integrity of membranes, and plays a role in facilitating cell signaling and communications.

Recent research added a new dimension to the mechanism of cholesterol in interaction with mycobacterium such as tuberculosis and leprosy. Mycobacterium possesses cholesterol receptor, say [C.sub.m] that tries to enter the macrophage of a cell through the cell membrane. A human cell receptor, say [C.sub.h], regulates the transcriptional expression of a gene that codes for Tryptophan-Asperate containing coat (TACO) protein which is responsible for the survival of mycobacterium within cells, Figure (5). The two receptors [C.sub.m] and [C.sub.h] with cholesterol-rich membrane domains helps to create a junction between mycobacterium and macrophage. This results in allowing mycobacterium to enter and survive within macrophages so they will not deplete into the cell. Gatfield and Pieters reported that TACO protein, associated with the membrane cholesterol and cell depleted cholesterol, were unable to internalize mycobacteria. The molecular mechanism through which cholesterol initiates this process is still poorly understood. However, agents can be designed to target the cholesterol-mediated entry of M. tuberculosis may be developed as tuberculosis therapeutics, http://cat.inist.fr/?aModele=afficheN&cpsidt=15473877

1-1-2 Mitochondria

Mitochondria are central components of our cells that generate the majority of our energy from nutrients. But their weak side is that, through their normal activity, they generate unstable chemicals that harm both the mitochondrion itself and other components of the cell. This resulting damage is thought to play a important role in aging.

Mitochondria are called the powerhouses of the cell. They are membrane enclosed organelles found in most eukaryotic cells (eukaryotic cells are in all animals except bacteria and cyanobacteria). They absorb the nutrients, break them down and then release energy called ATP, for the cell. The process of releasing energy is known as cellular respiration, which is associated with chemical reactions needed for the growth of the cell. Mitachondria are very small organelles. Some cells has one mitochondrion and others have several thousand mitochondria. Cells for transmitting nerve impulses have fewer mitochondria than muscle cells that need high energy. The numbers of mitochondria are adjusted depending on the energy needed by the cell. Mitochondria can move, grow, and combine with other mitochondria inside the cell. Figure (6) is of a mitochondrion with the outer and inner membranes. The purpose of Cristae is to increase the surface area inside the cell for more chemical reaction, when required. The matrix inside the mitochondria is fluid. Inside the matrix, oxygen is combined with protein to digest the food molecules, and the water inside the matrix, takes the digested food to feed the cell. Mitochondria are the only places in the cell where oxygen is used to digest the food molecules. Calcium may also be controlled by mitochondria.

Mitochondria have their own independent genome, the material of which is known as mitochondrial DNA (mtDNA) which we'll talk about it.

One cell may have several thousand mitochondria, Figure (7).

1-1-3 Nucleus

The cell nucleus is a huge storeroom of biochemical information. It is the brain of the cell and the core for direction and coordination of the cell's reproductive and metabolic activities. The nucleus is the largest organelle of a cell. Cells with a nucleus are called eukaryotic cells because eukaryotic means, "possessing a true nucleus immersed inside the cell". Plants and animals have nuclei, where organisms such as bacteria do not. The nucleus is about two to five micrometers long in diameter. It is surrounded by two membranes that form the nuclear envelope, see Figure (9). Most of the cell's genes are located in the nucleus. The nucleus contains DNA, RNA, a nucleoplasm, and a nucleolus. The two main parts of the nucleus are the nucleolus and the nucleoplasm. The nucleolus is usually visible as a dark, round spot in the nucleus. It helps in the formation of ribosomes. The nucleolus is made up of proteins and RNA. It is the site of ribosomal ribonucleic acid (rRNA) synthesis.

1-1-4 Cytoplasm

There are two parts of the cytoplasm of a cell; the upper part and the lower part. The upper part contains organelles such as the nucleus, the mitochondria, centrosomes, and ribosome. The lower part is the cytosol which is a complex mixture of the cytoskeleton, dissolved molecules, filaments, and water that fills much of the volume of a cell. The cytoskeleton is a network of protein filaments that are responsible for the movement and support of the cell. It also and give the cell its shape and outline. The cytoplasm has many different molecules dissolved in solutions such as fatty acids, sugars, and amino acids that are used to keep the cell working. Waste products are also dissolved in the cytoplasm before they are taken in by vacuoles and sent out of the cell. Another different cytoplasm is called the nucleoplasm, which is of different composition and only found inside the nucleus. The nucleoplasm holds the cell's chromatin and nucleolus. It is not always present in the nucleus. When the cell divides, the nuclear membrane dissolves and the nucleoplasm is released. After the cell nucleus has reformed, the nucleoplasm fills the space again.

The Cytoplasm is made up of proteins, amino acids, vitamins, nucleic acids, ions, carbohydrates, sugars, and fatty acids. All of the functions for cell expansion, growth and replication are carried out in the cytoplasm.

1-1-5 Lysosomes

Lysosomes are the cells' garbage disposal system. They are membrane-bound vesicles that contain hydrolytic enzymes that digest particles or cells such as bacteria taken into the cell by phagocytes. Hydrolytic enzymes are formed in the endoplasmic reticulum by the end result of the interaction of proteins, nucleotic acids, lipids and carbohydrates in the cell. After the bacterium is engulfed in a vacuole (a small cavity in the membrane or the cytoplasm), vesicles containing lysosomal enzymes combine with it. The destruction of bacteria releases hydrogen and reduces the pH of the enzyme of the lysosome. The effect of the reduction in the pH activates the enzymes. The lysosomes are then split into more secondary lysosomes and this results in the destruction and recycling of the bacteria. Lysosomes also degrade worn out mitochondria. The process of digestion is accomplished in three stages: bacteria or foreign bodies that enter the membrane will be encircled by the membrane itself, then the encircled membrane will be pinched off from the cells outer membrane to produce an endosome. Then the lysosomes will fuse with the endosome to degrade the contents.

Figure (10) shows the membranes, lysosomes, mitochondria, components of endoplasmic reticulum, and Golgi apparatus.

There are other garbage disposal systems called "peroxisomes" which are similar to the lysosomes, but they are much more dynamic and can replicate by enlarging and then dividing. Peroxisomes have enzymes that rid the cell of toxic peroxides such as Hydrogen peroxide ([H.sub.2][O.sub.2]).

1-1-6 Ribosomes

Ribosomes are the protein synthesizers or the protein builders of the cell they connect amino acids in long chains. Ribosomes are found in many places around the nucleus of the cell. They are floating in the cytoplasm (cytosol). Some ribosomes are found on the endoplasmic reticulum and they are called the rough endoplasmic reticulum, see Figure (9) above. A ribosome has two separated pieces or subunits called 60-S (large) and 40-S (small). When the cell needs to make protein, mRNA (the messenger RNA) is created in the nucleus. The mRNA is then sent into the cell and the ribosomes. When it is time to make the protein, the two subunits come together and combine with the mRNA. The subunits lock onto the mRNA and start the protein synthesis, http://www.biology4kids.com/files/cell_ribos.html.

The 60-S/ 40-S model works fine for eukaryotic cells. Prokaryotic cells have ribosomes made of 50-S and 30-S subunits. It's a small difference. Scientists have used this difference in ribosome size to develop drugs that can kill prokaryotic microorganisms that cause diseases, Figure (11).

(Continues...)

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