Anti-aging Flashcards

1
Q

UV damage to DNA results in

A

DNA repair/apoptosis

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2
Q

UV damage to keratinocytes results in

A

epidermal turnover due to cytokine production, growth and migration

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3
Q

Photoaged skin has extensive damage to

A

dermal connective tissue

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4
Q

UV irradiation induces expression of certain members of ____ family, which ______

A

MMP (matrix mellanoproteinase)

degrade collagen and other ECM proteins comprising dermal connective tissue

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5
Q

Major structural protein in dermal extracellular matrix

A

Collagen I

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6
Q

Dermal fibroblasts synthesize

A

Procollagen

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7
Q

2 primary pathways by which UV irradiation alters dermal collagen

A
  • stimulation of collagen breakdown->fragment, disorganized collagen
  • inhibition of procollagen synthesis–>loss of collagen content
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8
Q

Pathways that control procollagen expression

A

TGF-b

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9
Q

Collagen-degrading enyzmes ____ are produced in _____ and diffuse to _____, and this diffusion may be aided by

A

MMP-1, 3, 9
epidermis
dermis
direct binding of MMPs to collagenous ECM

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10
Q

Cells respond to excessive UV-induced damage via activation of

A

transcription factors
NF-Kappa B
AP-1
p53

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11
Q

Direct absorption of UVB photons leads to

A
  • cyclobutane pyrimidine dimers
  • pyrimidine (6-4) pyrimidone photoproduct

replication of damaged DNA –> mutations

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12
Q

UVB induced mutations

A

C->T, CC->TT at dyprimidine sites

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13
Q

UVA is most commonly associated with

A

oxidative damage

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14
Q

Main mutations of long wave UVA

A

G->T transversions

presumably arising through mechanisms involving oxidized DNA bases

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15
Q

main DNA product from UVA damage through oxidative mechanism

A

production of O2 singlet->8-oxo-guanine

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16
Q

Cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts alter the structure of DNA, and consequently,

A

inhibit polymerases

arrest replication

17
Q

Dimers may be repaired by

A

photoreactivation

nucleotide excision repair

18
Q

role of p53 gene

role of p53 transcription factor

A

tumor suppressor gene
major role in protection of cells from DNA damage

phosphoprotein regulates expression of stress response to genotoxic stress

19
Q

genotoxic stress causes

A

p53 nucleoprotein accumulates, binds to DNA to activate transcription

20
Q

p53 regulates cell cycle progression by

A
  • arresting in late G1 (stimulates synthesis of inhibitors of cyclin-dependent kinases) to promote DNA repair
  • triggering apoptosis
21
Q

Most p53 mutations are in ____ domain, which causes

A

DBD (DNA-binding core domain)

it to be unable to bind to DNA, transcription of target genes that code repair factors prevented

22
Q

Scientists propose MPF, which is

A

Mutation protection factor

ability of sunscreen to reduce DNA damage following UV exposure and attenuate epidermal expression of p53

23
Q

critical event leading to activation of p53

A

phosphorylation of N-terminal domain

24
Q

Protein kinases known to target transcriptional activation domain of p53

A

MAPK family

ATR/ATM/CHK1/CHK2/DNA-PK, CAK

25
Q

Heart of the problem of UV induced immunosuppression

A

elevation of IL-10

26
Q

Methods to attenuate signs/symptoms of photoaging

A

Retinoic acid
antioxidants
estrogens
growth factors/cytokines

27
Q

mode of action of All Trans Retinoic Acid (tretinoin)

A

nuclear hormone receptor agonist

binds to nuclear transcription factors

28
Q

Tretinoin facilitates _____ and stimulates ______ within _______ of sun exposed skin

A

ability to prevent collagen loss
stimulate new collagen formation
papillary dermis

29
Q

RAR binds _____ and ____, RXR binds _____

A

RAR: RA and 9-cis RA
RXR: 9-cis RA

30
Q

Retinoic acid receptors bind to _______ regions of DNA, therby initiating __________

A

hormone response elements

ligand-dependent gene transcription