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Aging > Ex2 L9 - Nutrient Sensing > Flashcards

Ex2 L9 - Nutrient Sensing Flashcards

1
Q

What are the cellular macronutrients?

A

carbohydrates, lipids, and proteins

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2
Q

Cells sense the —— and respond to —— by ——-

A

sense the abundance of macronutrients and respond to scarcity by mobilizing nutrient stores

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3
Q

What are the four key pathways/groups of the nutrient sensing network?

A

IGF-1
mTOR
AMPK
Sirtuins

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4
Q

Why are the signals and regulation of metabolic pathways so important?

A
  • byproducts cause damage over time (oxidative stress, ER stress, mitochondrial dysfunction, all lead to aging)
  • careful nutrient sensing prevents overutilization of nutrients (not too much or too little)
  • nutrient-sensing becomes dysregulated in aging and disease
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5
Q

What is mTOR?

A

mammalian target of rapamycin

  • nutrient sensor that also responds to cellular stress
  • regulates (increases) cell growth, proliferation, and survival
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6
Q

How is mTOR activated and inhibited?

A
  • activated by nutrient abundance
  • inhibited by nutrient depletion, exercise, and DNA damage/cellular stress
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7
Q

What happens to mTOR with age? What have studies shown?

A
  • hypothalamic mTOR activity increases with age (associated with late-life obesity)
  • lower mTOR activity correlates with longer lifespan in animal models, but acute inhibition also impairs healing and causes insulin resistance
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8
Q

What is Rapamycin?

A
  • FDA approved mTOR inhibitor called Sirolimus
  • derived from fermented soil
  • immunosuppressive and anti-proliferative effects
  • inhibiting mTOR mimics exercise
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9
Q

How does Rapamycin effect aging/what have the studies shown?

A

in mice:
- reduces age related disease and extends lifespan
- intermittent administration extends lifespan

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10
Q

What are the risks of long term use of Rapamycin?

A
  • infection due to immunosuppression
  • metabolic impairment (insulin secretion/sensitivity)
  • low dose studies show limited side effects
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11
Q

What is AMPK?

A

AMP-Activated Protein Kinase
- energy sensor (measure of energy depletion) that regulates many cellular metabolic processes

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12
Q

How is AMPK activated?

A
  • activated by increased AMP: ATP ratio (energy depletion) or exercise
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13
Q

What are the actions of AMPK?

A

stimulates:
catabolic pathways like…
- fatty acid oxidation
- glucose uptake via GLUT4 (insulin not required)
- autophagy (recycling things for resources)

inhibits:
anabolic pathways like…
- protein synthesis via inhibition of mTOR
- glycogen, cholesterol, and fatty acid synthesis

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14
Q

What happens to AMPK with age?

A

activity decreases with age

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15
Q

What is Metformin?

A
  • antidiabetic drug that lowers blood glucose in part by activating AMPK
  • mimics exercise (which also activates AMPK)
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16
Q

What did studies show about the effects of metformin?

A
  • increase lifespan in rodents
  • more studies underway
17
Q

What are the risks of Metformin?

A
  • risk for lactic acidosis (due to overproduction or underuse of lactic acid)
  • overactivation of AMPK is linked to cardiac hypertrophy
18
Q

What is the definition of caloric restriction?

A

10-40% reduction in calories without malnutrition or deprivation of essential nutrients

19
Q

What is the effect of caloric restriction on aging? Why does it occur?

A
  • shows delayed onset of age-related disease (especially cancer) and extended lifespan in some animal model, but not seen directly in humans
  • results from increasing AMPK and decreasing mTOR (both of which mimic exercise) via nutrient depletion
20
Q

Describe the monkey experiment that demonstrated caloric restriction?

A

monkeys were fed a 30% calorie restructed diet for 20 years
- reduced age-related disease like cancer, diabetes, heart disease
- one of two studies reported increased lifespan
- Canto and Owen were two of the famous monkey brothers on different diets

21
Q

What was the CALERIE study?

A
  • Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)
  • 218 normal/moderately overweight adults
  • goal was to follow a diet with 25% restriction for 2 years (low compliance)
  • average 10% weight loss that was sustained for 2 years after
  • reduced risk factors for age related disease (lower BP and cholesterol)
  • improved sleep, mood, sexual function, life quality
  • but also saw slight reduction in bone mass, brief anemic episodes
22
Q

What is intermittent fasting and what are the important factors in performing it?

A
  • pattern of eating involving restricted meal schedules
  • the timing of the fast is important: meals are restricted to an 8-10 hour window related to circadian rhythms
23
Q

What does fasting do to metabolism?

A

promotes lipolysis, which produces ketones

24
Q

What are ketones helpful for?

A
  • more efficient energy source than glucose
  • may protect against age-related metabolic damage in the CNS
25
Q

Caloric restriction and intermittent fasting both…

A

alter the activity of nutrient sensing networks

26
Q

What is hormesis?

A

a process that exhibits a biphasic dose response

27
Q

What is the hormetic zone? Give an example.

A

the zone in which there is a favorable response to a stressor or toxin
- there is an amount of ROS that is good and has benefits, but when you are below or above that amount, there are damaging effects

28
Q

What are Sirtuins?

A

nutrient sensors that allow pathways to be mediated within the hormetic zone
- family of histone deacetylases that “pack” DNA during cell division and regulate gene expression

29
Q

What activates sirtuins?

A
  • increase NAD+ (energy depletion)
30
Q

Sirtuins can contribute to…

A

increased lifespan in rodent models, but there is a greater impact on healthspan

31
Q

The FDA does not classify —— as a ——-

A

does not classify aging as a disease

32
Q

Byproducts of nutrient metabolism can cause ——– ——– over time via:

A

cellular aging
via: oxidative stress, ER stress, mitochondrial dysfunction

33
Q

Nutrient sensing ——– in aging and disease

A

becomes dysregulated

Aging (16 decks)

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