Physiology of Aging Flashcards
What is aging?
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
What Age is Considered ‘Old Age’?
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)
What are the characteristics of aging?
- 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
What is not completely known about the physiological changes that occur with aging?
- 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)?
Theories of Aging
- Evolutionary
- Genetic and Protein Dysfunction
- Free Radical Damage
- Cell Senescence
What are the hallmarks of aging
- primary hallmarks: causes damage
- Antagonist hallmarks: responses to damage
- integrative hallmarks: culprits of the phenotype
Genomic Instability effect on aging
primary hallmark
* Genetic damage from multiple exogenous and endogenous sources
* Reduced DNA repair mechanisms and accumulation of damaged DNA in later life
What are Reactive Oxygen Species (ROS)
Free radical-containing reactive oxygen species generated mainly in the mitochondria (ETC) damaging lipids, proteins and DNA:
* superoxide
* hydrogen peroxide
What are antioxidants
Antioxidant Enzymes:
* superoxide dismutase (SOD)
* catalase (CAT)
* glutathione (GSH) peroxidase
What is the impact of altering antioxidant gene expression?
Alterations in antioxidant gene expression increases lifespan in some animal models
Telomere attrition effect on aging
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
What is the impact of epigenetic modifications on aging?
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
What is the impact of protein homeostasis on aging?
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
What are the responses to damage that might lead to aging?
- deregulating nutrient sensing
- mitochondrial dysfunction
- cellular senescence
Describe the effect of deregulation of nutrient sensing on aging
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)
Describe the effect of mitochondrial dysfunction on aging
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?
Effect of Cellular Senescence on aging
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
Integrative hallmarks of aging
- stem cell exhaustion
- altered intercellular communication
Effect of stem cell exhaustion on aging
- HSCs are Hematopoietic stem cells (blood)
- MSCs are Mesenchymal stem cells (bone)
- IESCs are mammalian intestinal epithelial stem cells
Effect of altered intercellular communication on aging
What are some physiological changes that occur?
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
Oral, Dental, Vision and Olfactory Changes with Aging
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
Gastrointestinal Changes with Aging
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
Skeletal Muscle Changes with Aging
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)
Bone Changes with Aging
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
Cardiovascular Changes with Aging
alterations in ability to perform activities
* Decreased cardiac muscle fibres and hypertrophy
* Lower heart rate and maximal output
* Increased vascular resistance
* decreased anabolism
Pulmonary Changes with Aging
- Reduction in lung function and VO2 max
- Loss of diaphragm and inter-rib muscle strength; changes in chest wall
Renal Changes with Aging
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
Skin Changes with Aging
- Thinning of skin layers
- Changes in collagen structure; superficial laxity
- Irregular pigmentation
- Reduction in 7-dehydrocholesterol (less vit D synthesis in skin)
Cognitive Changes with Aging
- Less receptors but increased sensitivity
- Reduction in short-term memory, encoding and retrieving, executive function
- varies greatly
Immune System Changes with Aging
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)
What is the HPH system?
Hypothalamus-Pituitary Hormone System
* master regulator development, growth, puberty; maintenance of homeostasis
* “pacemaker” that signals the onset and termination of each life stage
Role of hypothalamus in the H-P system
Integrates information
* sympathetic and parasympathetic function
* behaviours – eating, fear, sexual
* endocrine function – secretes hormones that act on pituitary
Role if the pituitary in the H-P system
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
role of adrenal gland of the HPA axis
hypothalamic-pituitary-adrenal axis
* medulla – epinephrine/norepinephrine act on sympathetic neural system to change blood pressure, metabolism
* cortex – glucocorticoids (cortisol, corticosterone), mineralocorticoids (aldosterone), androgens
HPA Axis and Aging
decrease in functioning of HPA axis with age due to decline in hormones and/or alterations in feedback mechanisms
Neuroendocrine changes and aging
- HPA axis
- HPG axis estrogen and testosterone
- appetite and thirst
An Example of a System-Wide Effect of Aging
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
Effects of Aging on Energy Expenditure
- 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
factors involved in the pathogenesis of the physiological anorexia of aging and energy expenditure.
Pathological Mechanisms of Anorexia of Aging
- Poor oral health; dysphagia
- Mental health and cognitive function
- Medications
- Diseases of the gastrointestinal tract
- Cachexia of disease
- Inflammation
Treatment of Anorexia of Aging
Appetite stimulating pharmaceuticals mostly not effective
* Modifiable factors: treatable pathological causes, social factors related to obtaining and preparing food
* nutrition support
nutrition support for anorexia of aging
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)
When is oral nutrition support reccomended?
- undernourished older adults (increase energy, protein and micronutrient intake)
- prior to and after surgery (particularly with hip fracture)
- risk of pressure sores (bedridden)
