Cellular Aging Process Overview

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Questions and Answers

What is a primary characteristic of the aging process at the organismal level?

Decreased susceptibility to disease

Increased resistance to stress

Reduced physiological function (correct)

Increased tissue function

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

Decreased permeability due to structural changes

Increased membrane fluidity

Reduced saturated fatty acids

Increased permeability due to structural changes (correct)

What is a primary characteristic of senescent cells?

Increased number of multinucleated cells (correct)

Decreased number of lysosomes and Golgi

Decreased -galactosidase activity

Reduced size of the nucleus and nucleoli

What is an implication of increased chromatin condensation during cellular aging?

Decreased efficiency of DNA repair Signup and view all the answers

What is the significance of lipofuscin accumulation in aging cells?

It is a sign of cellular waste accumulation Signup and view all the answers

What is a major cause of somatic mutations leading to cancer?

DNA damage from endogenous and exogenous sources Signup and view all the answers

What is a mitochondrial change that occurs during cellular aging?

Decrease in the number of cristae Signup and view all the answers

Which cellular mechanism is primarily responsible for arresting the growth of cells with potential cancer-causing events?

Cellular senescence Signup and view all the answers

What is the 'good news' regarding cancer as presented in the content?

Genes have evolved to protect against cancer Signup and view all the answers

What is the consequence of decreased lysosomal activity in aging cells?

Accumulation of cellular garbage Signup and view all the answers

What is a key distinction between apoptosis and necrosis?

Apoptosis is a natural developmental process while necrosis is always due to trauma Signup and view all the answers

What effect can molecules secreted by senescent cells have on normal tissue?

They disrupt normal tissue differentiation Signup and view all the answers

In humans, how many telomeres are present in a typical somatic cell?

92 Signup and view all the answers

Cellular senescence, or arrested cell growth, is an example of 'good news' because it:

prevents cells from dividing uncontrollably and becoming cancerous Signup and view all the answers

What is the repeating nucleotide sequence found within human telomeres?

TTAGGG Signup and view all the answers

How does dietary restriction after adulthood typically affect the lifespan of lab animals?

It leads to increased lifespan Signup and view all the answers

What is the primary function of telomeres in a cell?

To protect the ends of chromosomes 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 is a common cause of a cell undergoing senescence?

Short or dysfunctional telomeres Signup and view all the answers

What occurs when telomeres become critically short in normal somatic cells?

The cell undergoes senescence and stops dividing Signup and view all the answers

What is the role of telomerase in cancer cells?

To maintain telomere length and allow continued proliferation Signup and view all the answers

What is the consequence of tumor cells losing the p53 checkpoint function in the context of telomeres?

The cells continue to divide without telomeres leading to genomic instability Signup and view all the answers

What is the 'molecular clock' mechanism linked to telomere shortening based on the content?

It measures the number of times a cell has divided Signup and view all the answers

What does the term 'genomic instability', linked to telomeres, refer to?

Uncontrolled rearrangement and mutations in chromosomes Signup and view all the answers

According to the provided information, what is the effect of a poor environment, such as dietary restriction, on an organism's resource allocation?

It increases maintenance (survival) while decreasing growth and/or reproduction. Signup and view all the answers

In laboratory animal studies involving mutations of insulin/IGF, what is a typical observation regarding lifespan?

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

In mammals, the insulin/IGF-1 signaling pathway involves which of these?

An insulin receptor, IGF-1 receptor, and an insulin-receptor-like receptor. Signup and view all the answers

What is a potential health consequence of a mild reduction in the function of the insulin receptor (IR) gene?

Type 2 (non-insulin dependent) diabetes. Signup and view all the answers

The somatotropic axis involves the interaction between what key components?

The anterior pituitary gland, growth hormone (GH) and IGF-1 produced by the liver. Signup and view all the answers

Based on the information provided, what effect did the deletion of one copy of the IGF-1 receptor gene have on mice?

Increased resistance to oxidative stress and increased mean lifespan, primarily in females. Signup and view all the answers

According to the content, what are telomeres?

The protective caps at the end of chromosomes. Signup and view all the answers

In the context of p53 alleles in a mouse strain, how is a 'm' allele defined?

It denotes a mutation. Signup and view all the answers

Study Notes

Cell Ageing Process

Cell ageing is a biological process that transforms a healthy, fit organism into one that is less healthy.
This process is characterized by reduced tissue/physiological function, increased susceptibility to age-related diseases, and decreased resistance to physical and psychological stress.
The molecular and physiological aging process, like IGF and p53 signaling pathways, are involved.
Telomeres are associated with cellular aging.
Cellular aging is a response to damage or stress. It leads to cell death (apoptosis) or arrested cell growth (cellular senescence).

Cellular Aging

Cellular aging involves a balance between good and bad news. Good news is that it prevents cancer; bad news is that it promotes aging.
The process of cellular aging is the body's response to damage and stress which leads to cell death (apoptosis).
It can also lead to arrested cell growth (cell senescence).

Objectives

Understand the molecular and cellular aging process, and its characteristics.
Understand the molecular and physiological aging process, including signaling pathways (e.g., IGF and p53).
Understand the connection between telomeres and cellular aging.

What is Aging?

Aging transforms a healthy, fit organism into one that is less healthy, losing their vitality and fitness.

Aging is a Biological Process

Aging is a process converting a healthy organism into a less healthy one, related to its environment.

Changes in the Plasma Membrane

Structural changes in the plasma membrane lead to changes in permeability.
Reduced membrane fluidity is due to a higher level of saturated fatty acids.

Nuclear Changes

Chromatin becomes more condensed (more cross-links between histones), making DNA damage less likely to be repaired.
This leads to cellular senescence.

Cytoplasmic Changes

Cytoplasmic volume increases with age.
Lipofuscin (age pigment) accumulates in non-dividing cells.
This pigment is yellow-brown in color.

Mitochondrial Changes

The number of folds (cristae) in mitochondria decreases.
The number of mitochondria decreases.

Lysosomal Changes

Lysosomal activity decreases, leading to the accumulation of cellular garbage (e.g., lipofuscin).
Release of enzymes leads to cell death.

Pre-programmed Cell Death (Apoptosis)

Apoptosis is different from necrosis, which is caused by external factors (trauma).
Apoptosis is an internal process (cellular suicide) with non-random DNA breaks (180 base fragments).
Apoptosis is a natural process of development, like the disappearance of interdigital tissue.

Cellular Aging Responses (Yin and Yang)

Cellular responses to aging are a dual process.
Good aspects prevent cancer; bad aspects promote aging.

Evolution of Long-Lived Organisms

Cell division is risky!
The lifespan of single-celled organisms is minimal.
Longer lifespans occur in multi-cellular organisms, including post-mitotic tissues.

Cancer

Cancer risk increases exponentially with age.
(Somatic) mutations fuel cancer development.
DNA damage, from both endogenous and exogenous sources, causes mutations.

Genes Involved in Cancer Protection

Genes evolved to protect from cancer development (tumor suppressor genes)
Damaged cells are caused to die or arrest growth due to tumor suppressor genes.
This process is known as apoptosis or senescence.

Tumor Suppression and Aging

A balancing act between protection from cancer and aging.

Senescence Morphology

Senescent cells are flattened, enlarged with increased beta-galactosidase activity.
Nucleus and nucleoli increase in size.
Number of multinucleated cells increases, and the number of lysosomes, Golgi and cytoplasmic microfilaments increases.

Cellular Senescence

Cellular senescence is the process of cell growth arrest in response to potential cancer-triggering events and DNA damage.
Stress/damage signals and short/dysfunctional telomeres trigger senescence.
Chromatin instability and oncogenes are other causes.

Molecules Secreted by Senescent Cells

Senescent cells secrete molecules that disrupt normal tissue differentiation.
Examples include milk production by mammary cells.

Cellular Senescence (Cellular Aging)

Cellular senescence is cellular aging, involving a gradual change in cells shape and morphology from young to aged appearance.

Molecular & Physiological Mechanisms of Aging

Dietary restriction after adulthood reduces the effects of aging and increases lifespan in various lab animals.
Insulin/IGF-1 signaling pathway genes are implicated in aging because they regulate metabolism and stress responses, and affect maintenance functions.

Integrating Molecular Mechanisms with Life-History Theory

Insulin/IGF-1 pathway regulates trade-offs between growth and maintenance.
Poor environmental conditions, like dietary restriction, increase maintenance functions (survival) and decrease reproductive rates.
Good environmental conditions increase growth and reproduction activities and decrease maintenance functions.
Lab animal studies show that mutations in insulin/IGF-1 pathways do not lead to extended lifespans.

Role of Insulin-Like Signaling

Is the role of insulin-like signaling evolutionarily conserved in various organisms, such as nematodes or flies?

Insulin-Like Pathway in Drosophila

This pathway involves insulin-like ligands, receptors (DAF-2), and downstream signaling pathways, such as PI3K and AKT, culminating in increased longevity.
Does it control aging? (Question)

Insulin/IGF-1 Signaling and Aging in Mammals

Worms and flies have one insulin/IGF receptor.
Mammals have insulin receptors, IGF-1 receptors, and insulin/receptor-like receptors.
Mild reduction in IR gene function contributes to type 2 diabetes (non-insulin-dependent diabetes).

IGF-1, Insulin-like Growth Factor 1

IGF-1 is a hormone that plays a role in cell survival, growth, puberty, and gonadal function, and reduced adiposity.

IGF-1 Receptor and Lifespan

IGF -1 receptor regulates lifespan and resistance to oxidative stress in mice, according to Holzenberger (2002)

p53 Gene, Cancer Risk, and Aging in Mice

p53 alleles affect mouse survival rates and rates of tumor development.

Telomeres and Aging

A connection is hypothesized between the length of telomeres and aging.

What are Telomeres?

Telomeres are repetitive DNA sequences at the ends of chromosomes.
They contain thousands of repeating TTAGGG sequences.
Humans have 92 telomeres (one on each end of each chromosome).

Telomerase and Senescence

Telomerase levels in somatic cells are low. This leads to telomere shortening with each cell division.
Short telomeres signal cells to stop dividing (senescence).

Telomerase and Cancer

Telomerase is active in cancer cells.
This allows cancer cells to maintain telomere length without shortening, resulting in immortality.

Short Telomeres and Growth Arrest

Short telomeres can trigger growth arrest via p53 DNA damage checkpoints.

Tumor Cells and p53 Loss

Tumor cells often lose p53 (the tumor suppressor gene).
This loss of p53 leads to cell division without stopping at telomere checkpoints.
This genomic instability promotes tumorigenesis (tumor development).

Telomere Function

Telomeres protect chromosomes and separate one chromosome from another in the DNA sequence.
Without them, chromosome ends are improperly "repaired". This leads to chromosome fusion and massive genomic instability.

Telomere Function (cont.)

Telomeres act as a "clock", regulating cell division cycles. Telomeric sequences shorten with each DNA replication cycle.
Telomere shortening causes cellular senescence.

Telomeres & Aging

Healthy human cells have a finite cell division capacity, which decreases with age.
Telomere shortening may be the molecular mechanism that counts cell divisions and triggers cellular senescence or growth arrest, leading to human aging.

How Does Telomerase Work?

Telomerase is active in germ cells, immortalized cells (in vitro), the vast majority of cancer cells and, possibly in some stem cells.
High telomerase activity is a defining characteristic of germ cells, stem cells, epidermal skin cells, and cancer cells.
Immortal cells lack normal telomere shortening and have permanently active telomerase.
Examples of immortal cells include cancer cells and some stem cells.

Human Aging

The Greek myth of Tithonus illustrates the dilemma of living longer without maintaining youth.
Living longer without maintaining youth is not ideal.

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Description

This quiz explores the biological concept of cellular aging, highlighting the physiological changes that occur as organisms age. Understand the molecular pathways like IGF and p53 that play a role, and learn about the balance between beneficial and detrimental effects of this process. Delve into the implications of telomeres and cellular responses to damage and stress.