Cellular Aging Process and Mechanisms

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Questions and Answers

What is the primary biological effect of the aging process on an organism?

Transformation into a less healthy and less fit state. (correct)

Enhancement of tissue and physiological functions.

An increase in resistance to environmental stress.

Conversion to a more efficient and healthier state.

What is a key characteristic of senescent cells?

Decreased size of the nucleus and nucleoli

Decreased number of lysosomes and cytoplasmic microfilaments

Flattened and enlarged morphology with increased -galactosidase activity (correct)

Reduced -galactosidase activity

Which of the following is NOT a typical characteristic of cellular aging?

Decreased resistance to stress.

Increased susceptibility to disease.

Reduced tissue and physiological function.

Increased repair of damaged DNA. (correct)

What change in the plasma membrane is associated with cellular aging?

Decreased membrane fluidity due to increased saturated fatty acids. Signup and view all the answers

According to the provided material, what is a significant factor that fuels cancer development?

Somatic mutations due to DNA damage Signup and view all the answers

What is a key alteration observed in the nucleus during cellular aging?

Increased condensation of chromatin. Signup and view all the answers

What role do tumor suppressor genes play in preventing cancer?

They cause cells to enter senescence or apoptosis. Signup and view all the answers

What mechanisms can induce cellular senescence?

Stress signals, DNA damage, and oncogene activation. Signup and view all the answers

What change happens to cellular lysosomes during the aging process?

Decreased activity, causing cellular waste accumulation. Signup and view all the answers

What effect does dietary restriction after adulthood have on lifespan, according to the text?

It reduces the effects of aging and increases lifespan. Signup and view all the answers

Which of the following specifically describes apoptosis?

Cell death initiated by an internal trigger, with DNA fragmentation into 180 base pair lengths. Signup and view all the answers

What is the relationship between cancer risk and age?

Cancer risk rises exponentially with age. Signup and view all the answers

What does the term 'cell senescence' refer to in the context of cellular aging?

Arrested cell growth. Signup and view all the answers

What is the dual role (Yin and Yang) of cellular senescence?

It can prevent the development of cancer but also contributes to the aging of cells. Signup and view all the answers

What is the primary function of cellular senescence?

To arrest cell growth as a response to potential cancer-causing events Signup and view all the answers

What could be the potential impact of molecules secreted by senescent cells?

Disrupt normal tissue differentiation. Signup and view all the answers

What is the repetitive DNA sequence found in human telomeres?

TTAGGG Signup and view all the answers

How many telomeres are present in a typical human cell?

92 Signup and view all the answers

What is the effect of telomere shortening on normal somatic cells?

It causes cells to enter senescence and stop dividing. Signup and view all the answers

What is the role of telomerase in cancer cells?

It maintains telomere length, allowing continuous cell proliferation. Signup and view all the answers

What is the primary function of telomeres in cellular biology?

To protect the ends of chromosomes from fusion and instability. Signup and view all the answers

What can happen when a cell loses the function of p53 and continues to divide despite having short telomeres?

It leads to genomic instability, chromosomal rearrangements, and promoting tumorigenesis. Signup and view all the answers

According to the provided content, what is the 'clock' that limits the number of times a cell can divide?

The length of the telomeres Signup and view all the answers

What is the cellular process that occurs when telomeres shorten to a critical length?

Cellular senescence Signup and view all the answers

What is the primary effect of a poor environment, such as dietary restriction, on the trade-off between growth and maintenance according to life-history theory?

It increases maintenance while reducing growth and/or reproduction. Signup and view all the answers

In lab animal studies, what is typically observed in insulin/IGF mutant organisms with life-span extending mutations?

They do poorly and do not show evidence of long lives. Signup and view all the answers

What is the effect of a mild reduction of function of the IR (insulin receptor) gene on health?

It leads to type 2 (non-insulin dependent) diabetes. Signup and view all the answers

What is the primary function of the somatotropic axis?

Mediating the effects of growth hormone via IGF-1. Signup and view all the answers

What was observed in mice heterozygous for a deletion of the IGF-1 receptor gene in the study by Holzenberger (2002)?

They had increased lifespan in females and resistance to oxidative stress. Signup and view all the answers

What is the relationship between the p53 gene and aging in the discussed mouse model?

The different alleles of p53 gene can affect cancer risk and aging. Signup and view all the answers

In the context of aging, the content suggests that insulin/IGF-1 signalling pathway genes are associated with:

Processes related to metabolism, stress responses, and maintenance. Signup and view all the answers

What was the conclusion regarding the relationship between insulin signalling and aging?

The role of insulin signalling on aging is still unclear. Signup and view all the answers

Study Notes

Cell Ageing Process

Cellular aging is a response to damage or stress.
This response can manifest as cell death (apoptosis) or arrested cell growth (cell senescence).
Aging is a biological process that transforms a healthy organism into one that is less healthy.
Cellular aging is important in regulating the cell cycle, including the prevention of cancer.

Objectives

Understanding the aging process at the molecular and cellular levels, including characteristics.
Understanding the molecular and physiological aging process, such as IGF and p53 signaling pathways.
Establishing the association between telomeres and cellular aging.

What Is Aging?

Aging is a biological process.
It converts a healthy organism into a less healthy one.

Aging

Reduced tissue/physiological function.
Increased susceptibility to disease (age-related diseases).
Reduced resistance to stress (both physical and psychological).

Changes in the Plasma Membrane

Structural changes lead to changes in permeability.
Less fluid due to an increase in saturated fatty acids.

Nuclear Changes

Chromatin becomes more condensed (increase cross-links, disulfide bonds between histones).
Implication: DNA damage less likely repaired.
Cells in culture eventually stop growing (senescence) due to changes in factors regulating the cell cycle.

Cytoplasmic Changes

Increased volume with age.
Lipofuscin (age pigment) found in non-dividing cells (e.g., nerve and muscle cells).
Lipofuscin appears as yellow-brown granules.

Mitochondrial Changes

Decrease in the number of folds (cristae).
Decrease in the number of mitochondria.

Lysosomal Changes

Reduced activity leads to the accumulation of cellular garbage (e.g., lipofuscins).
Release of enzymes leads to cell death.

Pre-programmed Cell Death (Apoptosis)

Apoptosis vs. Necrosis
- Necrosis: external cause (trauma), random DNA breaks
- Apoptosis: internal cause (cellular suicide), non-random 180 base fragments
Apoptosis as a natural developmental process (e.g., interdigital tissue, neurons).

Cellular "Aging" Responses: Yin and Yang

Good news (prevents cancer).
Bad news (promotes aging).

Evolution of Long-Lived Organisms

Life span varies between single-celled organisms, multi-cellular organisms with post-mitotic cells, and organisms with renewable tissues.
Cell division is risky.
The risk of cancer increases with age.

Cancer

Cancer risk rises exponentially with age
Driven by somatic mutations.
Mutations from endogenous & exogenous DNA damage.

Tumor Suppression & Aging

Genes protecting from cancer (tumor suppressor genes)
Damaged cells die or arrest growth (apoptosis or senescence).
An evolutionary balancing act between cancer protection and cellular aging.

Senescence Morphology

Senescent cells become flattened, enlarged, and exhibit increased β-galactosidase activity.
Larger nucleus and nucleoli.
More multinucleated cells.
Increased lysosomes, Golgi, and cytoplasmic microfilaments.

Cellular Senescence

Cellular senescence arrests growth in response to potential cancer-causing events.
- Chromatin instability
- DNA damage
- Short/dysfunctional telomeres
- Oncogenes
- Stress/damage signals

Molecules Secreted by Senescent/Aged Cells

Disrupt normal tissue differentiation; example: milk production by mammary cells.

Molecular and Physiological Mechanisms of Aging

Dietary restriction after adulthood reduces aging effects and increases lifespan in lab animals.
Insulin/IGF-1 signaling pathway genes are strongly implicated in aging effects (regulate metabolism & stress responses, influence maintenance functions).

Integrating Molecular Mechanisms with Life History Theory

Insulin/IGF-1 ('growth' hormones) pathway strongly regulates growth and maintenance trade-offs.
Poor environment (e.g., dietary restriction) favors maintaining survival and reduces growth and reproduction.
Conversely, good environment favors growth and reproduction but reduces maintenance.
Lab animal studies show that lifespan-extending mutations of insulin/IGF-1 pathway mutants perform poorly and do not show evidence of longer lives.

Telomeres and Aging

Humans have 46 chromosomes and 92 telomeres (one at each end of the chromosome).
Telomeres are repetitive DNA sequences at the ends of chromosomes.
Telomeres function in protecting chromosomes
Separating chromosomes.
Preventing their fusion, in turn, leading to genomic instability.
Telomeres act as a "clock".
The shortening of telomeric sequences is a regulator of a cell's division capacity.
Healthy human cells are mortal because they can divide a limited number of times; aging occurs from each division.
Telomere shortening may function as a molecular clock.

Telomerase and Senescence

In most somatic cells, telomerase expression is low or absent.
As cells divide, telomeres shorten, which gives signaling to cells to enter senescence.
Short telomeres signal cells to senesce (stop dividing).

Telomerase and Cancer

Telomerase is active in cancer cells allowing proliferation, and protecting telomere length.
Cancer cells often do not age.

Short Telomeres, p53 and Growth Arrest

Short telomeres trigger growth arrest via a checkpoint signaled by the p53 checkpoint mechanism.
If cells of a tumor still have p53, this works.
If tumor cells lose p53, then cell division continues, leading to chromosomal rearrangements.
Genomic instability can promote tumorigenesis

What do Telomeres do?

Protecting chromosomes.
Separating one chromosome from another in DNA sequence
Without telomeres, chromosome ends would be "repaired," leading to fusion and massive genomic instability.

Telomere Function (cont.)

Telomeres are a clock that regulates how many times an individual cell can divide.
Telomeric sequences shorten each time DNA replicates.
Once telomere shrinks to a certain level, cells stop dividing, slow down metabolism, age and die.

Telomeres & Aging

Healthy human cells are mortal because of a finite number of cell divisions. Dividing older each time they divide, until they age and die.
Telomere shortening may be a molecular clock, which counts the number of times a cell has divided and when telomeres are short, cellular senescence occurs.

How Does Telomerase Work?

Telomerase is active in germ cells, in vitro immortalized cells, a vast majority of cancer cells, and possibly some stem cells.
High telomerase activity exists in germ cells, stem cells, epidermal skin cells, follicular hair cells, and cancer cells.
Some cells are immortal due to switched-on telomerase.
Examples include blood cells and cancer cells.

Human Aging

The Greek god Zeus granted Tithonus the gift of immortality but not of perpetual youth.
Tithonus aged but could not die.
Tennyson's poem "Tithonus" reflects the desire for longer lives, even though it may be without youthful vitality.

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Description

Explore the intricate process of cellular aging, including the biological transformations and mechanisms involved. This quiz covers the implications of aging on health, the role of telomeres, and molecular pathways such as IGF and p53. Test your understanding of how cellular aging affects tissue function and disease susceptibility.