17 - Aging Flashcards
What is aging?
A multi-factorial complex process that is inevitable and irreversible. Process differs for each species.
When does aging start?
After development ends
What age is considered old age - older adult (senior), elderly
DRI age groups are 51-70 and >70.
Older adult (senior): >60 or 65
Eldery: >70 or 80
Hallmarks of aging
Primary hallmarks (causes of damage): genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis
Antagonistic hallmarks (responses): deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence
Integrative hallmarks (culprits of the phenotype): stem cell exhaustion, altered intercellular communication
What is genomic instability?
Genetic damage caused by endogenous or exogenous sources. Reduced DNA repair mechanisms and accumulation of damaged DNA.
What are ROS?
Superoxide and hydrogen peroxide generated in the mitochondria (ETC); damages lipids, protein, and DNA.
Antioxidant enzymes
Superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) peroxidase. Convert free radicals to H2O2 and then H2O.
Telomere attrition
Telomeres are chromosomal regions that are susceptible to DNA damage; decrease in length slightly with each replication; eventual impaired cellular replication. Telomerase repairs damage and maintains the length.
Epigenetic modifications
Occur throughout the lifespan from DNA methylation, histone modifications, etc. Adaptive changes in gene regulation that can lengthen or shorten longevity. Aging can cause epigenetic changes.
Protein homeostasis
Proper folding of proteins is needed to maintain protein function and mechanisms like lysosome autophagy, ubiquitin-proteasome pathway, and heat-shock mediated refolding are in place to monitor misfolded proteins. Aging decreases these processes, causing accumulation of unfolded and misfolded proteins.
Deregulation of nutrient sensing
Anabolic signalling (ex. amino acid sensing, insulin) accelerates aging and is downregulated with age (ex. mTOR). Dietary restriction also downregulates anabolic signalling, but through different mechanisms (AMPK and sirtuins) and are associated with longevity (not with human animals).
Mitochondrial damage
Reduced mitochondrial turnover and increased damage; causes ROS mediated damage, oxidative damage to proteins, lipid membranes, telomere attrition, and destabilization of respiratory chain complexes. Outcomes and be improved by resistance training and dietary restriction.
Cellular senescence
Cellular senescence is the stable arrest of the cell cycle, preventing proliferation of damaged cells and triggering removal by immune cells. Increased during aging, or decreased clearance. Also stress induced. Inhibits stem cell differentiation and intercellular communication with age.
How does muscle structure change with age?
Decrease in muscle size and imbalance between type 2 and type 1 fibres (type 2 decreases more). Reduction in innervation/nerve impulses and lowered muscle strength (upper body disproportionately affected).
Changes in senses
- Sensory cells are impaired, reducing ability of all senses
- Increased dental caries and brittleness
- Reduced saliva
- Changes in gum and teeth structure
Therefore, food intake is affected
Gastrointestinal changes
- Reduced gastric motility and emptying
- Stomach: increased stretch, decreased nitric oxide, atrophic gastritis (inflammation of lining)
- Small intestine: same transit time, but reduced absorption
- Liver: decreased size and blood flow, lower detoxification
Bone changes
- Resorption (osteoclast) >formation (osteoblast)
- loss of BMD
- decrease bone strength
- Accumulation of microfractures
Changes in cardiovascular and pulmonary function
- Increased vascular resistance
- Decrease heart rate and max output
- Decreased VO2 max/lung function
- Decreased cardiac muscle fibre and hypertrophy (not shrinkage, but function)
- Loss of diaphragm and rib muscle strength
How can cardiovascular changes be mitigated
- Movement is anabolic stimulus, so helps maintain body composition
Renal changes
- Function maintained, but slowed response to changes
- Reduced number of nephrons and decreased blood flow, so slowed filtration rate
- (impacts electrolyte balance)
Skin changes
- Lowered 7-DHC levels
- Irregular skin pigmentation
- Thinning
- Changes in collagen structure - superficial laxity
Cognitive changes
- Reduced receptors, but increased sensitivity
- Decrease short-term memory, encoding and retreiving, executive function
Immune changes
- Reduced bone marrow prod of RBCs
- Decreased resistance to infection
- Memory t-cells are retained, but new memory t-cells impaired (due to decreased t-cell maturation)\
- Increased autoimmune effect
What is the hypothalamus-pituitary hormone system?
It coordinates communication and responsiveness
- Regulates development, growth, puberty, homeostasis
- Signals onset and termination of each life stage
