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)
