Lecture 19: Stem Cell Ageing and Strategies for Rejuvenation
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Questions and Answers

What is primarily lost in vital organs as a result of aging?

  • Functional capacity (correct)
  • Nutritional absorption
  • Cellular volume
  • Structural integrity

Which of the following statements about stem cell changes with age is accurate?

  • All types of stem cells show equivalent growth with aging.
  • There is an increase in the number and functionality of stem cells.
  • Only the number of functional stem cells declines.
  • Stem cells accumulate mutations, affecting their function. (correct)

What physical change is NOT typically associated with aging?

  • Height increase (correct)
  • Increased inflammation
  • Presence of wrinkles
  • Weight gain

How does the repair capacity of tissues change with age?

<p>It slows down and becomes less effective. (C)</p> Signup and view all the answers

Which of the following is a consequence of changes in tissue properties with aging?

<p>Reduced muscle mass (B)</p> Signup and view all the answers

During which life stage is stem cell activity typically at its highest?

<p>Infancy and childhood (C)</p> Signup and view all the answers

What is a common disease risk associated with aging?

<p>Increased risk of cancer (B)</p> Signup and view all the answers

What is one significant outcome of calorie restriction observed in rats compared to those on a normal diet?

<p>Increased lifespan (B)</p> Signup and view all the answers

Which cellular function is restored by calorie restriction according to the findings?

<p>Cell-to-cell communication (B)</p> Signup and view all the answers

What role does Wnt signaling play in aging as indicated in the findings?

<p>It is a key pathway disrupted in aging. (B)</p> Signup and view all the answers

In the context of calorie restriction, what effect does it have on inflammation with age?

<p>Reverses the increase in inflammation. (C)</p> Signup and view all the answers

What method was primarily used in the study to analyze tissue composition in the research on calorie restriction?

<p>Single-cell sorting and transcriptional analysis (C)</p> Signup and view all the answers

What is a key outcome of aging on the functionality of hematopoietic stem cells?

<p>Dominance of certain clones (D)</p> Signup and view all the answers

Which intrinsic mechanism primarily contributes to the functional deterioration of stem cells with age?

<p>Accumulation of DNA damage (D)</p> Signup and view all the answers

How does the diversity of skin stem cells change with aging?

<p>Collapses leading to reduced diversity (A)</p> Signup and view all the answers

Which factor is associated with changes in cellular metabolic processes in aging stem cells?

<p>Alterations in gene expression (B)</p> Signup and view all the answers

What happens to mitochondrial efficiency in stem cells as they age?

<p>It decreases leading to dysfunction (C)</p> Signup and view all the answers

Which of the following represents a common misconception about aging stem cells?

<p>They maintain high diversity throughout life (D)</p> Signup and view all the answers

Which of these statements accurately describes the evolutionary perspective on post-reproductive age stem cell activity?

<p>Less evolutionary pressure exists to sustain stem cell activity (C)</p> Signup and view all the answers

What age-related change occurs in the variety of active hematopoietic stem cells?

<p>Collapse of diversity and dominance of specific clones (C)</p> Signup and view all the answers

Which epigenetic change is commonly associated with aging in stem cells?

<p>Accumulation of epigenetic markers indicating senescence (A)</p> Signup and view all the answers

How does age affect spermatogonial stem cells according to the findings?

<p>The decline in function is closely linked to changes in the niche rather than intrinsic cellular changes. (D)</p> Signup and view all the answers

What key finding resulted from the transplantation experiment involving aging spermatogonial stem cells?

<p>A degree of functional rescue was observed in old spermatogonial stem cells within a young testis environment. (B)</p> Signup and view all the answers

What does parabiosis surgery reveal about systemic factors in aging?

<p>Systemic factors from young animals can rejuvenate old animals' tissue regeneration abilities. (D)</p> Signup and view all the answers

What were the observed effects on muscle regeneration in old and young mice?

<p>Old mice displayed no capacity for muscle regeneration compared to young mice. (A)</p> Signup and view all the answers

What conclusion can be drawn regarding the intrinsic changes in stem cells with age?

<p>Intrinsic changes do not significantly impact the functional capacity of stem cells. (A)</p> Signup and view all the answers

In what way can systemic aging influences be demonstrated?

<p>Through parabiosis surgery connecting circulatory systems of young and old mice. (D)</p> Signup and view all the answers

What is indicated by the phrase 'systemic factors' in relation to aging?

<p>Circulating factors in the body can create synergies affecting aging processes. (C)</p> Signup and view all the answers

What aspect of stem cell function is primarily controlled by the aging process?

<p>External factors such as niche changes are the main regulators of stem cell function as age progresses. (A)</p> Signup and view all the answers

Which statement accurately reflects the relationship between systemic factors and muscle regeneration?

<p>Systemic factors from young organisms boost the muscle regeneration capacity of old mice. (B)</p> Signup and view all the answers

What is the primary purpose of transplanting young stem cells into old mice during experiments?

<p>To investigate if the microenvironment affects stem cell function. (D)</p> Signup and view all the answers

In the context of parabiosis experiments, what is the significance of pairing young and old mice?

<p>To provide control scenarios for evaluating systemic factors. (A)</p> Signup and view all the answers

What role does the stiffness of the tissue extracellular matrix play in stem cell behavior?

<p>It can alter stem cell behavior as it increases with age. (A)</p> Signup and view all the answers

Which observation would suggest that an aging phenotype is influenced by a dysfunctional microenvironment?

<p>Old stem cells regain function when placed in a young environment. (D)</p> Signup and view all the answers

What is a key factor in determining whether niche microenvironment influences stem cell activity?

<p>The age of the host organism. (B)</p> Signup and view all the answers

Which type of stem cells should be used when assessing the impact of the microenvironment through transplantation?

<p>Dysfunctional stem cells from old organisms. (C)</p> Signup and view all the answers

What does the term 'systemic factors' refer to in the context of stem cell behavior?

<p>Signals shared through the blood supply between animals. (C)</p> Signup and view all the answers

What is a potential outcome of transplantation experiments using old stem cells into young mice?

<p>Young mice may help improve the old stem cells' function. (C)</p> Signup and view all the answers

Which experimental design is utilized to ascertain whether the local niche impacts stem cell behavior?

<p>Transplantation into different age hosts. (C)</p> Signup and view all the answers

What might indicate that systemic factors do not affect stem cell behavior?

<p>An inability of old mice to influence the young mice's behavior. (C)</p> Signup and view all the answers

Flashcards

Vital Organ Decline

A decline in the functioning of vital organs, such as the heart, with age.

Increased Susceptibility to Diseases

An increase in the risk of developing various illnesses, including cancer and chronic diseases like diabetes, as we get older.

Changes in Tissue Properties

Changes in the physical properties of tissues, including increased tightness or stiffness (e.g., in skin) or the formation of scar tissue (fibrosis).

Reduced Repair Capacity

A reduced ability of the body to heal and repair itself, leading to slower wound healing and slower recovery from infections.

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Loss of Tissue Mass

The loss of tissue mass, particularly in muscles, as a natural consequence of aging.

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Decline in Stem Cell Numbers

A decrease in the number of stem cells in various tissues, leading to reduced regeneration and repair capabilities.

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Functional Decline of Stem Cells

Stem cells become less functional and less capable of dividing and differentiating into new cell types, even if their numbers remain relatively stable.

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Stem cell activity in reproductive years

Stem cells are responsible for maintaining tissues and undergo controlled activity during reproductive years.

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Stem cell activity in protected aging phase

The body's stem cells gradually decline in activity, moving into a phase focused on protecting existing tissues.

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Evolutionary perspective on stem cell decline

The decline in stem cell activity after reproductive years is explained by the evolutionary pressure for reproduction.

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Changes in blood stem cells with age

With age, hematopoietic stem cells (HSCs) exhibit decreased diversity, leading to a dominance of certain clones.

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Changes in Skin stem cells with age

Skin stem cells undergo a similar reduction in diversity with age, leading to a decrease in the overall regenerative capacity of the skin.

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DNA damage and telomere shortening in stem cell aging

DNA damage accumulation and shortening telomeres are factors contributing to the functional deterioration of stem cells with age.

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Mitochondrial dysfunction in stem cell aging

Mitochondria become less efficient with age, impacting stem cell function and contributing to the aging process.

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Epigenetic alterations in stem cell aging

Epigenetic alterations, changes in DNA packaging that don't affect the DNA sequence, influence stem cell function and aging.

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Metabolic changes in stem cell aging

Changes in metabolism, the set of chemical reactions that fuel the cell, contribute to the decline in stem cell function as we age.

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Testing Microenvironment Influence

Stem cells from a young mouse are transplanted into both a young and an old mouse. If the stem cells function worse in the old mouse, it suggests the aging environment in the old mouse is influencing stem cell behavior. This helps separate the influence of aging stem cells from the aging environment.

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Testing Microenvironment's Role in Regeneration

Stem cells from an old mouse are transplanted into both a young and an old mouse. If the old stem cells recover their functionality in the young mouse, it indicates that the aging environment is contributing to the stem cell decline in the old mouse.

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Parabiosis

Two animals are surgically connected to share their blood circulation, allowing the exchange of systemic factors like hormones and proteins.

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Young-Young Parabiosis

Parabiosis where both animals are young. This serves as a baseline for the comparison with young-old pairing.

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Old-Old Parabiosis

Parabiosis where both animals are old. This serves as a baseline for the comparison with young-old pairing.

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Young-Old Parabiosis

Parabiosis where a young animal is connected to an old animal. This allows investigation of how systemic factors from a young animal influence the aging of the old animal.

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Stem Cell Division and Aging

The ability of stem cells to divide into new cells decreases with age.

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Stem Cell Differentiation and Aging

The ability of stem cells to differentiate into specialized cell types decreases with age

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Stem Cell Repair and Aging

The ability of stem cells to repair damaged tissues decreases with age

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Niche Microenvironment

The environment surrounding stem cells, including neighboring cells, the extracellular matrix and signaling molecules, influences their behavior.

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What is Calorie Restriction?

Calorie restriction is a dietary strategy involving reducing caloric intake without malnutrition. It has been shown to extend lifespan in various species, including rats.

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How does Calorie Restriction Affect Senescence?

Calorie restriction has been linked to a reduction in markers of cellular senescence, suggesting it may decrease aging-related damage.

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What is the Impact of Calorie Restriction on Inflammation?

Calorie restriction can reverse age-related increases in inflammation and immune cells in various tissues.

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How does Calorie Restriction Affect Cell Communication?

Studies suggest that calorie restriction can restore age-related decline in cell-to-cell communication, potentially enhancing tissue function.

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What are the Molecular Changes with Calorie Restriction?

Calorie restriction has been shown to reverse transcriptional changes that occur with aging, specifically in gene expression and cell-to-cell communication.

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Age-Related Decline in Spermatogonial Stem Cells

The decline in the number of functional spermatogonial stem cells in the testes as an organism ages.

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Stem Cell Niche

The microenvironment surrounding stem cells, providing signals and support for their function.

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Tissue Regeneration

The ability of an organism to heal and regenerate tissues after injury.

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Stem Cell Aging

The study of how stem cells change with age and the factors influencing their function.

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Systemic Factors and Rejuvenation

Systemic factors from young animals can rejuvenate stem cell function and tissue regeneration in older animals.

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Niche Influence on Stem Cell Aging

Changes in the stem cell niche (microenvironment) contribute significantly to the decline of spermatogonial stem cell function with age.

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Stem Cell Transplant and Rejuvenation

Old spermatogonial stem cells can regain some function when transplanted into a young niche.

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Intrinsic vs. Extrinsic Factors in Stem Cell Aging

Changes within the stem cell itself are not the primary cause of age-related decline in spermatogonial stem cell function.

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Muscle Regeneration and Aging

The ability of muscle tissue to regenerate after injury is impaired in older mice.

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Study Notes

Lecture 19: Stem Cell Ageing and Strategies for Rejuvenation

  • Population Ageing: By 2061, the proportion of Australians aged 65+ is projected to increase from 14.0% to 22.4%.
  • Age and Tissue Decline: Age is associated with a reduced ability of tissues to maintain and regenerate, leading to various changes like organ decline.
  • Organ Decline: Nearly all vital organs experience functional decline with age. Cardiac failure is a significant cause of death related to this.
  • Susceptibility to Diseases: The risk of cancer increases with age, as does the incidence of chronic diseases like diabetes.
  • Tissue Stiffness: Some connective tissues lose elasticity (e.g., skin), while others become stiff, showing fibrosis.
  • Reduced Repair Capacity: Wound healing and repair processes become slower as we age. Damage to the gastrointestinal tract is a concern.
  • Tissue Mass Loss: Muscle mass decreases significantly with age.
  • Physical Changes: Age is associated with wrinkles, gray hair, and weight gain. Inflammation increases.
  • Stem Cell Decline and Mutations: Stem cells decline in many tissues with age and accumulate mutations, which impact their function.
  • Stem Cell Numbers Change: Some tissues show a reduction in stem cell numbers as we age, while others experience an increase, though with reduced functionality.
  • Stem Cell Activity Throughout Life: Stem cell activity varies throughout the lifespan, following a natural decline post-reproductive years.

Mechanisms Underlying Stem Cell Deterioration

  • DNA Damage and Telomere Shortening: Accumulation of DNA damage and shortening of telomeres contribute to cellular senescence.
  • Mitochondrial Dysfunction: Reduced mitochondrial efficiency with age.
  • Epigenetic Alterations: Age-associated changes in epigenetic markers.
  • Metabolic Changes: Alterations in cellular metabolic processes in stem cells.
  • Systemic or Circulatory Factors: Influence of the circulatory system on stem cell behavior.
  • Local Niche Microenvironment Growth Signals: Role of growth factors and signals from adjacent cells in regulating stem cell activity.
  • Tissue Extracellular Matrix Stiffness: Increased tissue stiffness (fibrosis) affects stem cell function/behavior.

Testing Stem Cell Dynamics

  • Testing Niche Microenvironment: Transplanting young stem cells into both young and old mice. If the stem cell function declines in the older mouse, the decline is due to niche-related factors. Conversely, old stem cells in a young mouse environment demonstrate niche effects on aging phenotype.
  • Testing Systemic Effects: Parabiosis experiments connecting the blood supply of young and old mice examined if systemic features affect the phenotype of aged stem cells.

Effects of Age on Specific Tissues

  • Spermatogonial Stem Cells: Reduced number of functional stem cells in the testes as age increases.
  • Muscle Stem Cells: Decreased number and function, as well as changes in differentiation toward a fibroblast-like lineage. This leads to fibrosis.
  • Other tissues: Decreased neurogenesis and angiogenesis in the brain; downregulation of hepatocyte proliferation.

Factors That Promote Aging Reversal

  • GDF-11 (Growth Differentiation Factor 11): When supplied to older mice, it increases muscle function and enhances tissue regeneration.
  • CCL-11: Upregulated in older, inhibits muscle function and regeneration.

Stem Cell Intrinsic Defects

  • Proteasome System Breakdown: Reduction in ubiquitin-proteasome system activity leads to toxic protein aggregates.
  • Unfolded Protein Response (UPR) Downregulation: Reduced ability to handle misfolded proteins.
  • Mitochondrial Damage: Mitochondria dysfunction often accompanied by DNA mutations affects energy generation.
  • Increased Reactive Oxygen Species (ROS): Increased ROS production due to protein aggregates and mitochondrial damage contributes to DNA damage and increased mutation rates.

Hematopoietic Stem Cell (HSC) Decline

  • Diversity Decline: Diversity in HSCs decreases with age.
  • Functional Decline: The number of active functional HSCs declines.
  • Skewed Differentiation Increased production of myeloid cells compared to lymphoid cells (imbalance in blood cell types).
  • Altered Niche Signals: Changes in signaling molecules in the HSC niche affect age-related changes.

Caloric Restriction

  • Calorie Restriction and Lifespan: Lower calorie diets are linked with increased lifespan.
  • Effects on Senescence: Calorie restriction has shown reduced senescence markers.
  • Cellular Communication/Inflammation: Reduced inflammation associated with the aging process.
  • Effects on Metabolism: Calorie restriction alters metabolic pathways affecting cellular function.

Strategies to Reverse Aging

  • Modulating Metabolism: Targeting mitochondrial function and increasing NAD availability.

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DEV30322 L19 PDF: Stem Cell Ageing and Strategies for Rejuvenation

Description

Test your knowledge about the effects of aging on vital organs and stem cell activity. This quiz covers topics such as the changes in tissue properties, disease risks, and the impact of calorie restriction as observed in research studies. Dive into the cellular mechanisms and physical changes associated with aging to enhance your understanding.

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