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NU FS 356 > Physiology of Aging > Flashcards

Physiology of Aging Flashcards

1
Q

What is aging?

A

Aging is a complex, multi-factorial process
* many factors interact simultaneously and operate at many functional levels
* inevitable, irreversible
* rate of aging and lifespan is different for each species

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2
Q

What Age is Considered ‘Old Age’?

A

depends on perception of age - aging starts after development stages ends
* DRI age groups: 51 to 70 years, >70 years
* Older adult (senior): >60 or >65 years
* Elderly: older adult or older older adults (ie >70 or >80)

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3
Q

What are the characteristics of aging?

A
  • Molecular and cellular changes
  • Decrease in regenerative capacity
  • Changes in tissue, organ and system functions
  • Decline in ability to respond to stress and environmental stimuli
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4
Q

What is not completely known about the physiological changes that occur with aging?

A
  • What changes are from just the aging process and which should be considered pathological?
  • Which physiological changes are inevitable versus which are related to changes in behaviours (and thus modifiable)?
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5
Q

Theories of Aging

A
  • Evolutionary
  • Genetic and Protein Dysfunction
  • Free Radical Damage
  • Cell Senescence
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6
Q

What are the hallmarks of aging

A
  • primary hallmarks: causes damage
  • Antagonist hallmarks: responses to damage
  • integrative hallmarks: culprits of the phenotype
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7
Q

Genomic Instability effect on aging

A

primary hallmark
* Genetic damage from multiple exogenous and endogenous sources
* Reduced DNA repair mechanisms and accumulation of damaged DNA in later life

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8
Q

What are Reactive Oxygen Species (ROS)

A

Free radical-containing reactive oxygen species generated mainly in the mitochondria (ETC) damaging lipids, proteins and DNA:
* superoxide
* hydrogen peroxide

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9
Q

What are antioxidants

A

Antioxidant Enzymes:
* superoxide dismutase (SOD)
* catalase (CAT)
* glutathione (GSH) peroxidase

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10
Q

What is the impact of altering antioxidant gene expression?

A

Alterations in antioxidant gene expression increases lifespan in some animal models

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11
Q

Telomere attrition effect on aging

A

primary hallmark (causes damage) - telomeres are chromosomal regions that are highly susceptible to damage (other type of DNA damage is random). Small losses of telomere length with replication can cumulate into impaired cellular replication
* telomerase repairs damage

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12
Q

What is the impact of epigenetic modifications on aging?

A

Primary Hallmark - causes damage
Aging itself can result in epigenetic changes
* Epigenetic modifications occur through out the lifespan (DNA methylation, histone modifications, other) causing adaptive response in gene expression which can shorten or extend longevity

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13
Q

What is the impact of protein homeostasis on aging?

A

primary hallmark - causes damage
Aging is associated with loss of repair mechanisms and accumulation of unfolded or misfolded protein
* Properly folded proteins essential for maintaining protein function
* Mechanisms to repair or remove unfolded and misfolded proteins: lysosome autophagy, ubiquitin-proteasome pathway, heat-shock protein mediated refolding

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14
Q

What are the responses to damage that might lead to aging?

A
  • deregulating nutrient sensing
  • mitochondrial dysfunction
  • cellular senescence
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15
Q

Describe the effect of deregulation of nutrient sensing on aging

A

Anabolic signaling accelerates aging (evolutionary theory) but then downregulation of anabolic signalling pathways occurs with aging leading to anabolic resistance.
* Anabolic signalling pathways for AA sensing, mTOR, FOXO
* Dietary restriction also downregulates anabolic signaling pathways but through different mechanism (AMPK and sirtuins) - associated with longevity (in non-human animals)

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16
Q

Describe the effect of mitochondrial dysfunction on aging

A

Reduced turnover of mitochondria and increased damage (Changes in ATP production)
* ROS mediated damage, oxidative damage to proteins, changes in lipid membranes, telomere attrition, destabilization of respiratory chain complexes
* Endurance training and dietary restriction can prevent?

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17
Q

Effect of Cellular Senescence on aging

A

With aging there is accumulation of senescent cells in some tissue and/or decreased clearance of senescent cells
* Undering normal conditions cellular senescence causes stable arrest of cell cycles which prevents proliferation of damaged cells and triggers removal by immune cells
* Telomere attrition, DNA damage

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18
Q

Integrative hallmarks of aging

A
  • stem cell exhaustion
  • altered intercellular communication
19
Q

Effect of stem cell exhaustion on aging

A
  • HSCs are Hematopoietic stem cells (blood)
  • MSCs are Mesenchymal stem cells (bone)
  • IESCs are mammalian intestinal epithelial stem cells
20
Q

Effect of altered intercellular communication on aging

A
21
Q

What are some physiological changes that occur?

A

tissues, organs, systems
* Oral, Dental, Vision and Olfactory Changes
* Gastrointestinal Changes
* Skeletal Muscle Changes
* Bone Changes
* Cardiovascular and Pulmonary Changes
* Renal Changes
* Skin Changes
* Cognitive Changes
* Immune System Changes
* Neuroendocrine Changes

22
Q

Oral, Dental, Vision and Olfactory Changes with Aging

A

Impacts food intake

  • Alteration in tooth and muscosal tissue structure in mouth
  • Increased dental caries and teeth brittleness
  • Reduced saliva secretion (↓ gland function)
  • Impaired function of sensory cells (reduced ability to smell, taste, hear and see
23
Q

Gastrointestinal Changes with Aging

A

Impact on satiety and nutrient needs
* Slower motility; delayed stomach emptying
* Stomach: decreased nitric oxide, increased stretch, atrophic gastritis
* Small intestine: transit time not affected but reduced absorption of some nutrients
* Liver: decreased size and blood flow; lower detoxification ability

24
Q

Skeletal Muscle Changes with Aging

A

Sarcopenia, disability
* Decease in size and number of muscle fibres (type 2 fibres affected more than type 1)
* Reduction in innervation
* Lowered muscle strength (upper body affected more than lower body)

25
Q

Bone Changes with Aging

A

loss of height and greater risk fracture with resorption > formation
* osteoclast activity > osteoblast activity
* loss of mineral density and protein, changes in mineral crystals properties
* decrease in bone strength
* accumulation of microfractures

26
Q

Cardiovascular Changes with Aging

A

alterations in ability to perform activities
* Decreased cardiac muscle fibres and hypertrophy
* Lower heart rate and maximal output
* Increased vascular resistance
* decreased anabolism

27
Q

Pulmonary Changes with Aging

A
  • Reduction in lung function and VO2 max
  • Loss of diaphragm and inter-rib muscle strength; changes in chest wall
28
Q

Renal Changes with Aging

A

impact on fluid ad electrolyte balance
* Reduced number of nephrons, slowed filtration rate, decreased blood flow
* Usually maintain normal function but slower to respond to sudden changes

29
Q

Skin Changes with Aging

A
  • Thinning of skin layers
  • Changes in collagen structure; superficial laxity
  • Irregular pigmentation
  • Reduction in 7-dehydrocholesterol (less vit D synthesis in skin)
30
Q

Cognitive Changes with Aging

A
  • Less receptors but increased sensitivity
  • Reduction in short-term memory, encoding and retrieving, executive function
  • varies greatly
31
Q

Immune System Changes with Aging

A

Functional capacity declines with age
* reduced bone marrow and production of blood cells
* lower resistance to infectious diseases
* autoimmune phenomena increase with age (body attacks itself)
* chronic mild inflammatory response (less T-cells made in thymus so decrease response to new infections)

32
Q

What is the HPH system?

A

Hypothalamus-Pituitary Hormone System
* master regulator development, growth, puberty; maintenance of homeostasis
* “pacemaker” that signals the onset and termination of each life stage

33
Q

Role of hypothalamus in the H-P system

A

Integrates information
* sympathetic and parasympathetic function
* behaviours – eating, fear, sexual
* endocrine function – secretes hormones that act on pituitary

34
Q

Role if the pituitary in the H-P system

A

releases hormones that have peripheral effects
* growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone (ACTH), LH, FSH, prolactin, oxytocin, antidiuretic hormone (ADH)

act on peripheral endocrine glands
* adrenal cortex, thyroid, gonads

35
Q

role of adrenal gland of the HPA axis

A

hypothalamic-pituitary-adrenal axis
* medulla – epinephrine/norepinephrine act on sympathetic neural system to change blood pressure, metabolism
* cortex – glucocorticoids (cortisol, corticosterone), mineralocorticoids (aldosterone), androgens

36
Q

HPA Axis and Aging

A

decrease in functioning of HPA axis with age due to decline in hormones and/or alterations in feedback mechanisms

37
Q

Neuroendocrine changes and aging

A
  • HPA axis
  • HPG axis estrogen and testosterone
  • appetite and thirst
38
Q

An Example of a System-Wide Effect of Aging

A

Anorexia of Aging
* 20% of older adults experience a reduction in appetite
* higher rates with chronic conditions, but occurs in healthy older adults and in the presence of adequate food availability

39
Q

Effects of Aging on Energy Expenditure

A
  • thermic effect of food is delayed or decreases may be due to ↓ rate of gastric emptying
  • physical acitvity goes down so loss of LBM
  • RMR is decreases with loss of LBM and decreased energy generation
40
Q

factors involved in the pathogenesis of the physiological anorexia of aging and energy expenditure.

A
41
Q

Pathological Mechanisms of Anorexia of Aging

A
  • Poor oral health; dysphagia
  • Mental health and cognitive function
  • Medications
  • Diseases of the gastrointestinal tract
  • Cachexia of disease
  • Inflammation
42
Q

Treatment of Anorexia of Aging

A

Appetite stimulating pharmaceuticals mostly not effective
* Modifiable factors: treatable pathological causes, social factors related to obtaining and preparing food
* nutrition support

43
Q

nutrition support for anorexia of aging

A

If undernourished and unable to meet needs through foods, nutrition support should be considered
* Oral nutrition support (ie nutrition drinks)
* Enteral nutrition (tube into stomach)
* Parenteral nutrition (intravenous)

44
Q

When is oral nutrition support reccomended?

A
  • undernourished older adults (increase energy, protein and micronutrient intake)
  • prior to and after surgery (particularly with hip fracture)
  • risk of pressure sores (bedridden)

NU FS 356 (21 decks)

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