Aging (18) Flashcards

1
Q

Are there reliable biomarkers for aging?

A

No…the best way to measure age is chronological age.

Usually measure the deather rate and the span of life at the population level

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2
Q

What is the Gompertz law of human mortality?

A

Death rate increases exponentially with age in a protected environment where external causes of death become negligable

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3
Q

What is mean lifespan defined as?

A

Age at which 50% of the members in a cohort have died

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4
Q

What is maximum lifespan?

A

Defined as age which oldest known member of a species has died (longest lived 10% of a population)

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5
Q

What is the programmed theory of aging?

A

Evolution selected genes for aging, to limit population size and to survive with limited resources

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6
Q

What is the mutation accumulation theory of aging?

A

Aging is a matter of neglect…random accumulation of alleles with late deletorious effects to accumulate over the generations with little or no effect

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7
Q

What is the antagonistic pleiotropy theory or aging?

A

Aging is a reflection of imperfection.

Some genes are selected for beneficial effects on reproductive and survival success early in life are not so good for later in life

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8
Q

What is the disposal soma theory of aging?

A

Age is a matter of resource allocation. Aging is driven by reduced soma maintenance and repair, as a trade-off of reproductive success

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9
Q

What is a method to delaying the aging process?

A

Increasing healthspan time…slowing down the aging process may delay the onset of aging related degenerative disorders (“compression of morbidity”

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10
Q

What are the 9 major hallmarks of aging?

A

1- genomic instability

2- telomere attrition

3- epigenetic alterations

4- proteostatic stress

5- deregulated nutrient sensing

6- mitochondrial dysfunction

7- cellular senscence

8- Stem cell exhaustion

9- altered intercellular communications

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11
Q

What does the free radical theory of aging predict?

A

That toxic byproducts of metabolism can damage cell components…notably the hydroxyl radical

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12
Q

What is the supportive evidence of free radical theory of aging?

A

Proven damage to DNA, lipids and proteins

Increase in abnormal mitochondrial with age

Acceleration of age with ionizing radiation

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13
Q

Why is the free radical theory of aging being challenged?

A

Because animals deficient in or overexpressing antioxidant enzymes do not generally have a longer lifespan

Naked more rats (live longer) have higher, rather than lower oxidative stress

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14
Q

What are the effects of mitochondrial dysfunction?

A

Energy depletion

Increased the propensity of mitochondrial permeability in response to stress…so there is an increase in apoptotic or necrotic cell death

Defective iron-sulfer biosynthesis…affects nuclear genome stability

Alters redox and ROS signaling

Affects global protein homeostasis

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15
Q

What is the cell senscence/ telomere shortening theory of aging?

A

Most somatic cells do not express telomerase and when telomeres get too short a double strand DNA break like DNA damage response is triggered and cells enter into senescence

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16
Q

What is teh somatic mutation theory of aging?

A

Age related acumulation of mutations

17
Q

What is the proteostatic stress theory of aging?

A

Protein synthesis rate is regulated by ribosome biogenesis, mRNA loading and the initiation and elongation steps in the translation process

With age, bad proteins are degraded through autophagy…and this overwhelms cell machinery

18
Q

True or False: Mice with defective growth hormone or growth hormone receptor live longer

A

True

19
Q

Does an increase or decrease in IGF-1/ insulin signaling extend lifespan?

A

Reduced

20
Q

How does activation of FOXO transcription factor benefit cell survival?

A

ROS detox

DNA repair

Cell cycle arrest

GLucose metabolism

Energy homeostasis

21
Q

Does an increase or decrease in mTOR signaling favor cell survival?

A

Reduced mTOR signaling

22
Q

What molecule can block mTOR signaling?

A

Rapamycin

23
Q

What is Larone syndrome?

A

Dwarfism…patients are almost cancer free, have less DNA damage in response to H2O2, decreased insulin levels and increased sesitivity to insulin, and are obese

They do not live longer

24
Q

What is FOXO 3A associated with?

A

Metabolic regulation and stress resistance

25
Q

What is CETP associated with?

A

Plasma lipid transport

26
Q

What is APO C3 associated with?

A

Component of VLDL

27
Q

What is TOMM40 associated with?

A

Mitochondrial protein import

28
Q

What is hutchinson Gilford progeria syndrome?

A

Aging disorder assoicated with: Increased DNA damage, epigenetic alterations, chronic p53 signaling, inflammation, metabolic alterations, autophagy deregulation, stem cell dysfunction, protin dyshomeostasis

29
Q

What are some successful interventions that resist the effects of aging?

A

Caloric restrictions, physical exercise, rapamycin