Name: telomere shortening and cell aging
Uploaded: 2023-04-30T18:28:50.000Z
Duration: 2 min 15 s
Channel: JoVE

K12 Standards

Louisiana Student Standards for Science

High School

Life Sciences

from-molecules-to-organisms-structures-and-processes

From Molecules To Organisms: Structures And Processes

HS-LS1-4

Replicative Cell Senescence

Most animal cells divide a finite number of times before they stop and undergo permanent cell cycle arrest.
In a mitogenic medium, for example, human fibroblast cells divide about 25-50 times. As a cell approaches this finite number of divisions, the rate of cell division slows down and finally halts with cells entering a permanent non-dividing state. This phenomenon is called replicative cell senescence.
Replicative cell senescence is a result of changes in the structure of telomeres. Telomeres are located at the ends of the chromosomes and consist of long repetitive DNA sequences and protein complexes.
In the absence of telomeres, chromosome ends could be recognized as double-strand breaks. These ends could fuse to one another forming abnormal structures like a ring chromosome. The telomeres act as caps, protecting the ends of the chromosomes from degradation by nucleases and preventing the aberrant fusion of chromosome ends to one another.
Shelterin is a telomere-associated protein complex that protects the chromosome ends.
Shelterin helps DNA ends form a lariat-like structure called a telomerase-loop, or T-loop. This T-loop masks the DNA ends, preventing degradation.
During cell division, telomeres are shortened by 25-200 bases due to the inability of the polymerase to completely replicate DNA ends. As the length of telomeres becomes shorter, the shelterin components are displaced from the telomere region. Shrinking of the telomere eventually destabilizes the t-loop conformation.
The change in the T-loop structure leaves the chromosome ends exposed, which are sensed as DNA damage by the DNA damage response pathway.
The persistent DNA damage response that ensues induces replicative cell senescence which helps limit genomic instability and malignant transformation.

replicative cell senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism&#39;s lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere &#8212; short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase &#8212; an enzyme that adds the telomeric repeat sequence and enables repetitive cell division; however, in adults, telomerase is active only in the cells that need to divide regularly.
Because telomerase is inactive in most human somatic cells, the length of the telomere decreases with every cell division. After a critical length, telomere shortening leads to permanent cell cycle arrest. This mechanism is assumed to protect against cancer development by limiting the abnormal proliferation of tumors; however, a rare mutation can activate telomerase, which reconstructs the telomere region, allowing the cells to proliferate. Thus, telomerase is a perfect target for specific anticancer therapy, as most cancer cells express telomerase while normal cells do not.
The relation between telomere length and tumor formation has been experimentally verified using oncogenic mice. Oncogenic mice are mouse models that have cancer-causing genes. When such oncogenic mice are crossed with telomerase-deficient mice that lack telomerase activity, the resultant progeny mice express shorter telomeres than the oncogenic parent. These progeny mice, when interbred, generate successive generations that have progressively shorter telomeres. The frequency of tumor formation is studied by treating the progeny mice with carcinogens at every generation. As per the results, the late generation mice with shorter telomeres exhibit a reduced frequency of tumor formation compared to the early generation mice that maintain longer telomeres. This proves that limiting the replicative capacity of cells suppresses tumor formation.

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism&#39;s lifespan while ...

Education

JoVE Core

Cell Biology

Unit 1

Cell Proliferation

KEY TERMS AND CONCEPTS

telomere shortening and cell aging

Replicative cell senescence is a form of cell aging linked to repeated cell division. As cells divide, their telomeres shorten. Telomeres are protective DNA caps at the ends of chromosomes.

When telomeres become too short, cells can no longer keep dividing in the same way. The cell enters senescence, a state in which it stays alive but stops dividing. This process helps explain how division limits can affect cell growth over time.

Telomere Shortening and Cell Aging

what is the cell cycle?

Cell Cycle Stages and Checkpoints

The cell cycle is the set of events that a typical eukaryotic cell goes through during its life. In somatic cells, it has two main stages: interphase and the mitotic phase. Interphase is the time when the cell grows, carries out basic metabolic functions, copies its DNA, and gets ready to divide. The mitotic phase comes next. During mitosis, the nucleus divides, and during cytokinesis, the cytoplasm divides. These steps produce two daughter cells that are identical to the original parent cell.

interphase

Cell Growth Phases Before Mitosis

Interphase is the part of the cell cycle when a eukaryotic cell grows and gets ready for mitosis. In a typical human cell, the full cell cycle lasts about 24 hours. Interphase makes up about 95 percent of that time and includes three stages: G1, S, and G2. After mitosis and cytokinesis, cells enter G1, or gap 1. During this stage, cells grow continuously and prepare for DNA replication. They are metabolically active and copy important organelles and biochemical molecules, including proteins. <br...

the cell cycle control system

Cell Cycle Checkpoints and Regulation

The cell cycle is controlled by checkpoints and regulator proteins that help cells divide in an orderly way. These controls monitor whether a cell is ready to move from one stage to the next. They help prevent division from continuing when conditions are not right. The control system depends on proteins that can either encourage or block progress through the cycle. Some of these regulators act as signals that push the cell forward. Others act as brakes that slow the cycle when problems are...

positive regulator molecules

Positive Regulators in Cell Growth

Positive regulator molecules help cells move through the cell cycle. The cell cycle is the series of steps a cell uses to grow and divide. These molecules act as signals that support progress through each stage. Two important examples are cyclins and cyclin-dependent kinases, or CDKs. Cyclins are proteins that rise and fall during the cell cycle. CDKs are enzymes that work with cyclins to help control cell-cycle events. Together, these positive regulators help the cell advance when conditions...

inhibition of cdk activity

How CDK Inhibitors Slow Cell Division

Cyclin-dependent kinase (CDK) inhibitors slow cell division by blocking CDK activity. CDKs are enzymes that help control the cell cycle, which is the series of steps a cell follows to grow and divide. When CDKs are inhibited, the cycle can pause instead of moving forward. The video focuses on this control point in cell growth. CDK inhibition is important because it helps regulate when cells enter the next stage of the cycle. By stopping CDK activity, cells do not continue dividing at the wrong...

s-cdk initiates dna replication

S-Cdk Starts the DNA Copying Process

S-Cdk starts the DNA copying process by triggering DNA replication. S-Cdk is a cyclin-dependent kinase that helps move the cell into S phase, the part of the cell cycle when DNA is copied. This step matters because the cell must begin replication at the right time. S-Cdk adds phosphate groups to target proteins, which changes their activity and helps turn on the machinery needed for DNA synthesis. The result is that replication can begin in a controlled way. This process is an important part...

m-cdk drives transition into mitosis

M-Cdk Triggers the Start of Mitosis

M-Cdk triggers the start of mitosis by helping a cell move from interphase into division. It is a key cell-cycle regulator that turns on the mitotic program at the right time. The M-Cdk complex includes a cyclin and a cyclin-dependent kinase. When this complex becomes active, it sends signals that push the cell into mitosis. This step helps control when chromosomes begin to condense and the nuclear changes of division can begin. Understanding M-Cdk is important because it links cell-cycle...

mitogens and the cell cycle

Mitogen Signals in Cell Division

Mitogens are signals that help cells move through the cell cycle. The cell cycle is the set of stages a cell follows to grow and divide. In many cells, mitogens are needed before the cell can enter division. These signals work through pathways inside the cell. One important route is the MAP kinase signaling pathway, which helps pass the mitogen message from the cell surface to the cell’s interior. This signaling helps the cell respond and continue through the cycle. Mitogens are closely tied...

Replicative cell senescence is a form of cell aging linked to repeated cell division. As cells divide, their telomeres shorten. Telomeres are protective DNA caps at the ends of chromosomes. When telomeres become too short, cells can no longer keep dividing in the same way. The cell enters senescence, a state in which it stays alive but stops dividing. This process helps explain how division limits can affect cell growth over time.

abnormal proliferation

Unchecked Cell Growth Patterns

Abnormal proliferation is a pattern of cell growth that does not follow normal control. In healthy tissue, cells divide only when they are needed. When that control is lost, cells can keep multiplying in an unusual way. This kind of cell growth can be seen in different settings. It may involve cells that divide too fast, too often, or when they should stop. The result is tissue that grows in a way that no longer matches the body’s normal balance. Understanding abnormal proliferation helps...

cells coordinate growth and proliferation

cells-coordinate-growth-and-proliferation

Cell Size Homeostasis and Checkpoints

Cells coordinate growth and proliferation to keep cell size under control. Growth increases cell mass, while proliferation creates new cells. Together, these processes help cells maintain size homeostasis, which means keeping a stable size over time. The cell cycle includes a checkpoint called the size checkpoint. At this point, the cell checks whether it has grown enough before it divides. This control helps connect growth with cell division, so cells do not become too small or too large. <br...

key terms and concepts

Learn how repeated cell division shortens telomeres and leads to replicative cell senescence, a state where cells remain alive but stop dividing.

Telomere Shortening and Cell Aging | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

Tennessee Academic Standards

Biology

From Molecules to Organisms: Structures and Processes

BIO1.LS1.6

Minnesota Academic Standards in Science

9-12

Life Science

3.1.1 9L.3.1.1.3

Arizona Science Standards

HS.L1

HS.L1U1.22

Florida Department of Education

SC.912.L.16

SC.912.L.16.8

Nucleic Acids and Nucleotides

Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell&#39;s genetic blueprint and have instructions for its ...

Nucleic Acid Structure

The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group ...

DNA Base Pairing

Erwin Chargaff&#x2019;s rules on DNA equivalence paved the way for the discovery of base pairing in DNA. Chargaff&#x2019;s rules state that in a ...

From DNA to Protein

The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of ...

The DNA Helix

Deoxyribonucleic acid, or DNA, is the genetic material responsible for passing traits from generation to generation in all organisms and most viruses. DNA ...

The Central Dogma

The central dogma explains the flow of genetic information from DNA nucleotides to the amino acid sequence of proteins.
RNA is the Missing Link Between ...

Genomic DNA in Prokaryotes

The genome of most prokaryotic organisms consists of double-stranded DNA organized into one circular chromosome in a region of cytoplasm called the ...

Genomic DNA in Eukaryotes

Eukaryotes have large genomes compared to prokaryotes. To fit their genomes into a cell, eukaryotic DNA is packaged extraordinarily tightly inside the ...

Overview

Deoxyribonucleic acid, or DNA, is the genetic material responsible for passing traits from generation to generation in all organisms and most ...

DNA Packaging

Overview

Eukaryotes have large genomes compared to prokaryotes. In order to fit their genomes into a cell, eukaryotes must pack their DNA tightly inside ...

RNA Structure

Overview
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form ...

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations ...

pre-mRNA Processing

In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or ...

Types of RNA

Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs ...

DNA as a Genetic Template

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised&#160; of nucleotides and proteins are ...

Transcription

Transcription is the synthesis of RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. ...

Translation

Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes ...

Ribosomes

Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that ...

tRNA Activation

Initiation of Translation

Termination of Translation

What are Cells?

Cell Diversity

The concept of a cell started with microscopic observations of dead cork tissue by Robert Hooke in 1665. Hooke coined the term &#34;cell&#34; based on the ...

Cells of the Epidermis

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Bone Cells and Tissue

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Gross Anatomy of Skeletal Muscles

The connective tissues play a significant role in arranging the muscle fibers into a hierarchical structure that forms a complete muscle. Consider a ...

Structure of Cardiac Muscles

Cardiac muscle, or myocardium, is a specialized type of muscle found exclusively in the heart. Its unique structural and functional characteristics enable ...

structure-and-organization-of-smooth-muscles

Structure and Organization of Smooth Muscles

In the human body, smooth muscle tissue is found lining the visceral and tubular organs such as the liver, lungs, blood vessels, and respiratory tract.
...

Chromosome Replication

Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone ...

Neurons: The Cell Body and the Dendrites

A typical nerve cell comprises three main components: the cell body, dendrites, and the axon. The cell body, also known as the soma or perikaryon, serves ...

Lampbrush Chromosomes

In 1882, Flemming observed lampbrush chromosomes (LBC) in salamander eggs. Later in 1892, R&#252;ckert observed LBCs in shark egg cells and coined the ...

Neurons: The Axon

The axon is a long, thin extended portion of the neuron that carries impulses from its cell body toward the effector cell.
Axoplasm, the axon&#39;s ...

Polytene Chromosomes

Polytene chromosomes are giant interphase chromosomes with several DNA strands placed side by side. They were discovered in the year 1881 by Balbiani in ...

Nervous Tissue: Neuron Types

Neurons, the fundamental units of the nervous system, can be classified based on both their structural and functional characteristics.
Structurally, ...

Euchromatin

The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions ...

Nervous Tissue: Glial Cells

Glial cells or neuroglia are non-neuronal cells in the nervous system that outnumber neurons. These include astrocytes, oligodendrocytes, microglia, and ...

Heterochromatin

Lymphoid Cells and Tissues

Lymphoid cells and lymphoid tissues are the two major components of lymphoid organs.
Lymphoid cells consist of immune system cells such as B and T ...

chromatin-position-affects-gene-expression

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the ...

Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The ...

Organization of Genes

Chromosome Structure

A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.
The centromere is a DNA ...

Construct an explanation based on evidence for how the structure of DNA determines the structure of proteins which carry out the essential functions of life through systems of specialized cells. Emphasis is on the conceptual understanding that DNA sequences determine the amino acid sequence and thus protein structure. Students can produce scientific writing, or presentations, and/or physical models that communicate constructed explanations.

HS-LS1-1

Characteristics of Life

Biology is a natural science that studies life and living organisms, including their structure, function, development, interactions, evolution, ...

https://cloudfront.jove.com/files/media/science-education/science-education-thumbs/10647.jpg

Levels of Organization

Biological organization is the classification of biological structures, ranging from atoms at the bottom of the hierarchy to the Earth&#x27;s biosphere. ...

The Scientific Method

The scientific method is a detailed, empirical problem-solving process used by biologists and other scientists. This iterative approach involves ...

Taxonomy

Taxonomy is the science of defining and naming groups of biological organisms based on shared characteristics. It uses a hierarchy of increasingly ...

Phylogeny

Phylogeny is concerned with the evolutionary diversification of organisms or groups of organisms. A group of organisms with a name is called a taxon ...

Develop and use a model to illustrate the hierarchical organization of interacting systems that provide specific functions within multicellular organisms. Emphasis is on functions at the organism system level such as nutrient uptake, water delivery, or organism movement in response to neural stimuli. An example of an interacting system could be an artery depending on the proper function of elastic tissue and smooth muscle to regulate and deliver the proper amount of blood within the circulatory system.

HS-LS1-2

Overview of Metabolism

Living cells constantly carry out various chemical reactions which are necessary for their proper functioning. These reactions are interlinked to one ...

Regulation of Metabolism

Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands ...

Positive and Negative Feedback Loops

Animal organs and organ systems constantly adjust to internal and external changes through a process called homeostasis (&#34;steady state&#34;). Examples ...

Functions of Life

Human life is characterized by a variety of functions that are essential for survival and well-being. These functions include metabolism, movement, ...

Requirements for Human Life

The Earth and its atmosphere have provided humans with air, water, and food, but these are not the only requirements for survival. Humans also require a ...

What is Homeostasis?

Maintaining homeostasis requires that the body continuously maintain its internal conditions. Each physiological condition has a particular set point, ...

Negative and Positive Feedback

Homeostatic Imbalance

Homeostasis is the maintenance of a stable internal environment within the body, which is crucial for the proper functioning of cells, tissues, organs, ...

pH Homeostasis

Acid-base homeostasis is essential for maintaining normal physiological activities in humans. The pH of various body fluids is strictly regulated because ...

homeostatic-imbalances-in-body-temperature

Homeostatic Imbalances in Body Temperature

Hyperthermia is an umbrella term for elevated body temperature that occurs when heat production exceeds the body&#39;s ability to dissipate it.
...

Regulation of Food Intake

The hypothalamus releases peptides influencing feeding behavior.
Two hypothalamic neuronal groups participate in this process.
Neuropeptide Y (NPY) and ...

Plan and conduct an investigation to provide evidence that feedback mechanisms maintain homeostasis in living organisms. Examples of investigations could include heart rate responses to exercise, stomate responses to moisture and temperature, root development in response to water levels, or cell response to hypertonic and hypotonic environments.

HS-LS1-3

What is the Cell Cycle?

The cell cycle refers to the sequence of events occurring throughout a typical cell&#8217;s life. In eukaryotic cells, the somatic cell cycle has two ...

Interphase

The cell cycle occurs over approximately 24 hours (in a typical human cell) and in two distinct stages: interphase, which includes three phases of the ...

The Cell Cycle Control System

Positive Regulator Molecules

Inhibition of CDK Activity

S-Cdk Initiates DNA Replication

M-Cdk Drives Transition Into Mitosis

Mitogens and the Cell Cycle

Use a model to illustrate the role of the cell cycle and differentiation in producing and maintaining complex organisms. Emphasis is on conceptual understanding that mitosis passes on genetically identical materials via replication, not on the details of each phase in mitosis.

Telomere Shortening and Cell Aging

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