2.3: Cells - Components and Functions

We can now use our understanding of body chemicals to examine cells in greater detail. In doing so, we will focus on the structures and corresponding functions in one cell that has the general features found in most cells (Figure 2.17). Specializations in cell structures and age changes in cells are described in Chaps. 3 through 15, along with the systems in which they are found.

Figure 2.17 Cell structure (Copyright 2020: Augustine G. DiGiovanna, Ph.D., Salisbury University, Maryland. Used with permission.)

Cell Membrane

The outer boundary of the cell is called the cell membrane. It consists of a double layer of phospholipid molecules that contains other lipid molecules and protein molecules. Some of these proteins have carbohydrate molecules extending outward from them (Figure 2.18).

The lipids and some proteins give the membrane strength to hold the cell contents together and regulate the continuous passage of substances into and out of the cell through the membrane. Other proteins and carbohydrates serve as identification markers for the cell, attach the cell to other cells or neighboring structures, or serve as cell membrane receptors. Receptors are like antennae that receive messages by binding messenger molecules. The cell membrane may also engulf particles and take them into the cell, a process called phagocytosis.

Cytoplasm

A very soft gel called cytoplasm lies within the cell membrane. Cytoplasm is mostly water, and it contains a large quantity and variety of dissolved ions and molecules. Its gel‑like consistency supports organelles, allowing them to function and interact properly. Cytoplasm also stores dissolved materials and granular substances. Finally, many chemical reactions occur in the cytoplasm. Some of them release energy, which may be transferred by ATP or other modified nucleotides to energy‑consuming reactions and activities in the cell.

Endoplasmic Reticulum

Membranes similar to the cell membrane extend throughout much of the cytoplasm. These membranes, called endoplasmic reticulum (ER), partition the cytoplasm much as walls, floors, and ceilings divide the inside of a building into rooms and corridors. The ER compartmentalizes the cytoplasm and regulates the movement of materials within it. Smooth ER also manufactures lipids (e.g., steroids). The other type of ER is called rough ER because its coating of granular structures makes it appear like rough sandpaper. The granules are called attached ribosomes, and they manufacture proteins that will be secreted from the cell. Other ribosomes, called free ribosomes, are suspended in the cytoplasm and manufacture proteins for use within the cell. Proteins destined for secretion are transported between layers of ER to a packaging area.

Golgi Apparatus

The protein‑packaging area is an organelle called the Golgi apparatus, which consists of stacks of containers made of membranes arranged like stacks of flattened bags. Like grocery bags being packed at a checkout counter, Golgi apparatus containers are filled with proteins destined for secretion. The Golgi apparatus also manufactures carbohydrates, some of which combine with proteins as they are packaged. Filled Golgi containers are transported to the cell membrane, where, like bubbles, they burst open and release their contents from the cell.

Vacuoles

Some proteins in the cell are stored in droplets of fluid surrounded by membranes. Other manufactured materials, as well as dissolved substances or particles taken in by the cell membrane, may be stored in a similar way. Such storage containers are called vacuoles. Vacuoles with special functions may have other names. For example, vacuoles containing proteins that help digest materials (i.e., digestive enzymes) are called lysosomes, and vacuoles containing substances that destroy certain toxins are called peroxisomes.

Mitochondria

Each mitochondrion consists of a double layer of membrane enclosing a small amount of liquid (Figure 2.19). Mitochondria are of various shapes and sizes.

Figure 2.19 Mitochondrial structure. (Copyright 2020: Augustine G. DiGiovanna, Ph.D., Salisbury University, Maryland. Used with permission.)

Many of the numerous chemical reactions in mitochondria convert one type of molecule to another. This activity helps provide a balance of molecules in the cell. Other related chemical reactions release energy. Mitochondria that receive oxygen release much more energy than is released by the cytoplasm. However, as in the cytoplasm, most of the energy released in mitochondria is placed into ATP molecules for transfer to energy‑consuming activities throughout the cell.

The energy in the ATP molecules originates in nutrient molecules in food. As the cell breaks down the molecules, carbon dioxide and other wastes are released. During these processes, electrons and hydrogen ions removed from the nutrients carry energy from the nutrients into the mitochondria. Then the electrons and ions are moved by regulated mechanisms along and through the inner mitochondrial membrane. The mechanisms are called electron transport and oxidative phosphorylation. At the end of these mechanisms, the electrons and hydrogen ions are combined with oxygen to form water while the energy they carried is used to make ATP.

A small percentage of the electrons and ions escape the ATP-producing mechanisms and combine with oxygen to form free radicals and ROS (e.g., *O₂^-, H₂O₂, *OH). From less than 1 percent to 5 percent of the oxygen used by mitochondria ends up in *FRs and ROS. The amount is determined by several factors including the type of cell, chemical conditions in the cell, and the age and condition of the mitochondria. Damaged and old mitochondria produce more *FRs and ROS. Though mitochondria contain antioxidants and enzymes to eliminate them, some ROS and *FRs escape from the mitochondria and cause damage in other parts of the cell or the body. The *FRs and ROS also damage the mitochondria, especially their inner membrane and their DNA. Mitochondrial DNA (mtDNA) damage is greatest in active non-dividing cells (e.g., heart, muscle, brain). Damaged mitochondria also produce less ATP. All these changes increase with age and may be a main cause of aging. (see Mitochondrial Theory and Mitochondrial DNA Theory below).

Microtubules and Microfilaments

Besides membranous organelles, the cytoplasm has long thin organelles that consist mainly of protein. Those shaped like tubes are called microtubules, and those shaped like fibers are called microfilaments. Like tent poles and ropes, both types of organelles provide internal support for the cell, forming the cytoskeleton (Figure 2.20). They also help the cell change shape and move, and help transport materials from place to place within the cell.

Figure 2.20 The cytoskeleton; microtubules and (Copyright 2020: Augustine G. DiGiovanna, Ph.D., Salisbury University, Maryland. Used with permission.)

Nucleus

The cytoplasm and its organelles are separated from an inner region of the cell by a double layer of membrane called the nuclear membrane. This membrane and the materials it surrounds constitute the nucleus. The soft gel in the nucleus (i.e., nucleoplasm) resembles cytoplasm. The highly convoluted DNA molecules it contains have several names, including chromosomes, chromatin, hereditary material, and genetic material. The information encoded in the DNA directs the construction and activities of the cell. The portion of the DNA directing the production of ribosomes is called a nucleolus. The portion of the DNA at one end of each chromosome is called a telomere. The telomeres are of different lengths on different chromosomes.

Genetic Control

Human cells have 46 chromosomes. Like the sentences in each chapter of a lengthy instruction manual, each chromosome has thousands of instructions. When an instruction is to be carried out, the nucleus makes an RNA copy of the instruction contained in the DNA. Accurate transcription is achieved by complementary base pairing. The RNA copy - messenger RNA (mRNA) - may be edited in the nucleus before being transported to the cytoplasm. Using other RNA molecules in ribosomes and in the cytoplasm, the instruction in the mRNA directs the assembly of amino acids to form a chain with a specific length, ratio, and sequence. These characteristics help determine the final shape and functions of the amino acid chain. After twisting, bending, and possibly combining with other amino acid chains, the amino acid chain is a finished protein molecule.

The length of DNA used to direct the formation of an amino acid chain is called a gene. Only some genes are used at any given time. One way a cell can prevent a gene from operating is by winding the DNA for that gene tightly. Masses of tightly wound DNA are called heterochromatin. Other gene activity is controlled by other genes, by messenger substances, and by conditions in and around the cell.

Some protein molecules are called structural proteins because they become structural components of the cell. Other protein molecules (enzymes) control the production of non-protein substances and regulate cell activities. Therefore, by directing the manufacture of structural proteins and enzymes, DNA controls all the structures and functions of the cell.

Cell Division

If a cell continues enlarging, it must eventually divide. Otherwise, the amount of cytoplasm and organelles it contains will become too large to be adequately served by its cell membrane and nucleus.

DNA Duplication

In preparation for division, a growing cell makes a copy of its DNA (Figure 2.21). Occasional errors occur during this process, but certain enzymes, acting like proofreaders, identify and correct nearly all these errors before duplication of the DNA is completed. It is noteworthy that similar enzymes can maintain the genes in an error‑free condition by repairing the DNA if it is damaged afterward.

Figure 2.21 Cell life cycle leading to cell reproduction (a) Life cycle (b) Reproduction by mitosis. (Copyright 2020: Augustine G. DiGiovanna, Ph.D., Salisbury University, Maryland. Used with permission.)

One error that is usually not corrected is the omission of part of each telomere. As a cell divides repeatedly during life, its telomeres become ever shorter in an age-related manner. Shortening of telomeres occurs at different rates among the chromosomes. Once the telomeres reach the minimum critical length, the cell is unable to divide again because it cannot make a complete copy of the remaining DNA, which contains essential genes. The reasons are not clear, but they may involve deleterious effects on chromatin structure or signals that inactivate genes needed for cell division.

Human telomeres consist of repeated segments made of six nucleotides (i.e., TTAGGG). Other animals and other organisms have different sequences and lengths in their telomere repeat units. Telomeres have diverse functions besides permitting complete replication of the essential DNA in a chromosome. Examples include attaching chromosomes to the nuclear membrane; preventing chromosomes from attaching to each other; protecting DNA from enzymatic attack; and influencing genetic activities.

Some cells can prevent shortening of their telomeres with each cell division. Examples include embryonic cells, sperm-producing cells, and cancer cells. Usually, such cells use the enzyme telomerase to rebuild the telomere during DNA replication. Some cells use mechanisms not requiring telomerase.

The effects of telomere shortening and telomerase on human aging are not yet known. Rapid telomere shortening is found in Werner's syndrome and in Down's syndrome, which are two syndromes that mimic rapid aging. Persons born with low birth weights who experience growth spurts (i.e., bursts of cell division) after birth, or people who experience growth spurts for any reason, may have especially short telomeres in their rapidly growing body parts because of the decline in telomerase after birth. Results for such individuals may include increased risk of high blood pressure because their kidneys may grow faster than normal or increased risk of atherosclerosis due to rapid cell proliferation in arteries injured by high blood pressure.

Maintaining or reinitiating telomerase production may be a main cause of cancer. If telomerase activity could be stopped in cancer cells, the cancer might be curable. Alternatively, if telomerase could be reactivated in specific cells where injury has occurred, better healing might result.

Mitosis

Once the cell has copied its DNA and has enough cytoplasm and organelles to divide, it partitions the DNA into two identical sets of genes. The cell then pinches itself into two cells, each of which contains one set of genes plus some of all the other cell components. This process, which results in cell reproduction, is called mitosis (Figure 2.21). In the early phase of mitosis, the cell winds its duplicated DNA strands into tightly coiled chromosomes (Figure 2.22). At the end of mitosis, portions of each chromosome are unwound so many genes become active again.

Figure 2.22 Chromosome structure. Chromosome structure during mitosis. Each side has a complete copy of the chromosome’s genes. The two sides separate at the centromere during mitosis, and each new cell receives a side. (a) The DNA in one telomere region is shown uncoiled, as it might exist outside of mitosis. (b) Chromosome with telomeres highlighted. (Copyright 2020: Augustine G. DiGiovanna, Ph.D., Salisbury University, Maryland. Used with permission.)

Besides maintaining efficient cells, the growth and reproduction of cells allow for growth, replacement, and repair of parts of the body. It is through these processes that a single microscopic cell (a fertilized egg) develops into a full‑grown person composed of trillions of cells. Cell growth and reproduction also allow for the replacement of skin cells and red blood cells, which are dying continuously, and for the healing of skin that has been cut or scraped.

Hayflick limit

In 1961, Hayflick and Moorhead reported that cells removed from the dermis of human skin and grown in laboratory vessels divide a certain number of times, stop dividing, and gradually die. Since then, this characteristic has been observed in many cell types from humans and other animals. It is now commonly called the Hayflick limit. Cells in laboratory vessels that stop dividing and eventually die said to undergo replicative senescence (RS).

The Hayflick limit shows three properties that seem to be related to aging. First, the number of divisions is negatively correlated with the XL of the species from which the cells originate (e.g., mice have 10-15 divisions, humans have 60 divisions, Galapagos turtles have 100 divisions or more). Second, the number of divisions is inversely proportional to the age of the person from whom the cells were taken. Third, the number of divisions is lower for cells from people who undergo changes like aging but at an abnormally young age (i.e., progeroid syndromes). Because of these and other factors, many scientists believed that the Hayflick limit was the key to age changes.

It has since become evident that aging does not result from a loss of ability of body cells to divide. Cells from even the oldest humans can divide 20 or more times when grown in laboratories. Also, many body cells lose their ability to divide in the process of differentiation (e.g., neurons, muscle), so loss of ability to divide does not equal old age or the approach of death of the cells. However, age-related changes occur in cells as they approach their Hayflick limit. Examples include enlargement, less motion, altered chromatin and nucleoli, and very short or absent telomeres. Therefore, aging occurs in cultured cells, and reaching the Hayflick limit is one indication that the cells are aging.

Scientists continue to debate the importance of the Hayflick limit to human aging. Some say it is an artificial phenomenon that occurs only in laboratory vessels. Others state that cells undergoing RS are different from cells that remain in the body. Also, the proportion of cells in the skin that have some features like RS cells is not related to the age of the person. Certain researchers believe that RS-like cells in the skin exist only in pathological conditions (e.g., arthritis, atherosclerosis, Werner's syndrome), not in normal aging.

Despite this controversy, the Hayflick limit and the process of replicative senescence has been studied intensively. Much research has focused on discovering how RS is controlled. Telomeres and telomerase may be an important key. Recent research showed that cells do not reach a Hayflick limit and RS when active genes for telomerase are placed into the cells. Many other factors, regulators, and possible mechanisms have been scrutinized and seem to be involved. As a result, this research has been helped by theories of aging and has contributed to further development and modification of these theories (see Biological Aging Theories below). These pathways seem to be related to age changes in the body and to regulating the growth of cancer.