Normal aging vs Disease

Question 1

Normal change with aging:

Answer 1

1. Lens of the eyes due lens stiffer and muscle weaker to maintain the shape to accomodation to focus on close or distant object.
2. Height due to compression of the vertebrae.

Question 2

Cellular factor in Aging:

Answer 2

• Altered intracellular communication (inflammatory processes)
• Decrease cell replication (stem cell)
• Mitochondrial dysfonction (increase formation of Free radical and ATP production altered)
• Loss of proteostasis, Cellular senescence
• Telomere shrink over time (DNA strains gaps)
• Genomic instability
• Deregulated nutrient sensing (calories)

Question 3

3 types of senescence:

Answer 3

1. Senescence due to normal aging
2. Disease-related senescence (Chronic disease/smoking)
3. Therapy-induced senescence (Chemotherapy/transplantation)

Question 4

Telomeres change with aging depend on the type of cell:

Answer 4

Somatic cells: Growth arrest, the cell stop divided. 
Germ cells (HIgh activity of Telomerase) 
Stem cells (do not lose length during life)

Question 5

Genes implicated in apoptosis:

Answer 5

Bcl-2 (block apoptosis)
APO-1/FAS (stimulates apoptosis)
MYC (stimulates apoptosis and cell proliferation)
p53 (stimulates wild types and block mutants–> growth arrest or apoptosis)

Question 6

Why are calories restriction can prolong lifespan?

Answer 6

1. Had an effect on the metabolism (decrease energy intake, temperature –> decrease inflammation, increase DNA repair, stem cell function.
2. Result in transcription factor skc-1, acting in neurons to release.
3. Sirtuins increases (proteins activate enzymes to protect against cellular damage/free radicals).

Question 7

Two proteolytic systems:

Answer 7

1. Ubiquitin Proteosome System

2. Lysosome Autophagy System

Question 8

Ubiquitin proteosome system:

Answer 8

Proteins misfolded or need to be destroyed are ubiquitinated (marked for destruction)

Question 9

Lysosome autophagy system:

Answer 9

Proteins are encapsulated and destroyed by lysosomal enzymes.

Question 10

Chaperones are:

Answer 10

Help proteins to have a folded structure.

Question 11

More the person do not do exercise and do not maintain a healthy weight, more the person lose years of life. Why is exercise is important?

Answer 11

• Muscle release cytokines (called myokines) into the circulation as communication factors. Theres myokines have effects on our adipose tissues, the liver, the pancreas and the growth of blood vessels. Exercise had a impact on the skeletal muscles, CNS (neuroplasticity) and the heart (lipolysis).
• Anti-inflammatory effect

Question 12

Peak bone mass vs fracture threshold:

Answer 12

160mg/cc vs 100mg/cc

Question 13

Normal bone turnover:

Answer 13

-Brokendown by osteoclasts and built back by osteoblast. (du to RANK ligand/RANK receptor)

Question 14

Osteoclasts are formed by:

Answer 14

from Macrophages

Question 15

Ligand on the surface of the osteoblast called:

Answer 15

RANK ligand bind to RANK receptor on the osteoclast (maintain equilibrium with stable rate of bone turnover)

Question 16

Why is Estrogen is a protective factor of osteoporosis?

Answer 16

Estrogen releases a blocking agent (osteoprotegerin) that block the interaction between RANK ligand and RANK receptor. So fewer osteoclasts are triggered.

Question 17

When estrogen level decrease (menopause), what happens with the bone turnover?

Answer 17

Less blocking of osteoclast formation, more break down the bone, increase the risk of osteoporosis.

Question 18

How is the Osteoclasts break down the bone?

Answer 18

Release HCL by his proton pump.

Question 19

With age, there are changes in the peak bone mass:

Answer 19

• Decreased replicative activity of osteoprogenitor cells
• Decreased synthesic activity of osteoblasts
• Decreased biologic activity of matrix bound growth factors.
• Reduced physical activity

Question 20

With menopause, there are changes in the peak bone mass:

Answer 20

• Decrease serum estrogen
• Increased IL-1, IL-6 and TNF level
• Increased expression of RANK and RANKL
• Increase osteoclast activity.

Question 21

Osteoarthitis is:

Answer 21

Chronic inflammation due to bone remodelling, cartilage breakdown, tissues damage and release of inflammatory mediators. (Hypertrophy of the bone, more macrophages)

Question 22

Risk factors for osteoarthritis:

Answer 22

Trauma at early age
Trauma with poor muscular support of the joint
Obesity