age sex and race 1 Flashcards by Tanya Unknown

what is CFR

case fatality rate - (total no of deaths/total no. cases) x 100

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cfr in males vs females for covid

higher in males than females

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link between ageing and degen. pathology - 5

dec function in molecules, cells, tissues, organs

inc age is risk factor for most chronic diseases - ncds burden inc

age related disorders are responsible for health care costs globally

markers associated with ageing are common to all organs - multimobility issues

geriatric syndromes like sarcopenia

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chronological age is a leading risk factor for … (12 oof)

congestive heart failure

myocardial infarction

dementias

stroke

most cancers

type 2 diabetes

renal dysfunction

chronic lung disease

osteoporosis

arthritis

blindness

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geriatric syndromes include … (5)

fraility

sarcopenia

falls

incontinence (pee leaking)

mild cognitive impairment

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decreased resilience examples include … (3)

delayed recovery after event

inc severity of infectious disease

impaired antibody response on vaccination

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what is senescence

irreversible cell cycle arrest - cells stop dividing but remain metabolically active

often in response to stress or damage

upregulate anti apoptotic pathways, releasing mediators, driving disease mechanisms

can refer to age of cell in person of any age

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is senescence good or bad

mechanism evolved for good - wound healing, wound regen, and tumour suppression

but contributes to inflammation, stem cell depletion, and tumour generation

activate SCAPs (Senescent Cell Anti-apoptotic Pathways)

which prevents cells from dying even when they are dysfunctional

neutral effects also like aging process and enhanced senescence

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what organelle alterations are caused by senescence - 3

abundance

enzymatic activity

permeability

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what biochemical alterations are caused by senescence - 3

buffer systems

membrane potential

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what are the two senescent cell antigens

surface markers

receptors

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what are the senescent cell anti-apoptotic pathways that promote its survival - 7

BCL-2 family

USP7

HSP90

PI3K-AKT

dependence receptors

p53 modulation

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process by which a normal cell becomes senescent + outcome

accumulated stress e.g. oxidative, damage e.g. mitochondrial, (inc with age)

forms senescent cell

upregulated anti apoptotic machinery
and
releases SASP, drives inflammation

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what is SASP and what does it cause

senescence associated secretory phenotype

pro inflammatory and tissue disruptive

released by senescent cells into local environment

potentially spread through circulation and endocrines, can enduce more senescent cells

drives inflammaging ( age inc, baseline inflammation inc)

causes ongoing amplification, underpins many ncds

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three phases of senescence biomarker/ therapeutic research

discovery - which proteins secreted? which population?

verification - which SASP detected in plasma?

validation - are biomarkers elevated with age/disease? reduced with treatments?

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2 classes of senescence-related drugs and what they do

senolytics - restore apoptosis to selectively clear senescent cells

senomorphics - modulate SASP aka change what is secreted

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how do senolytics work

selectively clear senescent cells by making them vulnerable to apoptosis by

disabling SCAPs - senescent cell anti apoptotic pathways

so cells now responsive to SASP - can induce apoptosis of senescent cells

howevs senescent do eventually reaccumulate as age, oxidative stressors, etc are still present so retreating needed

4 examples of senolytics

dasatinib

quercetin

fisetin

navitoclax

what other factors can inc likelihood of senescence - 7

uv light - dna damage

epigenetic changes

oncogenic stress

replicative stress

oxidative balance (oxidative stress: ROS)

mitochondrial dysfunction

HPA axis

(result of senesence depends on cell type and tissue function)

what is sarcopenia

change in appearance and physical performance of our muscle, age related

changes to appearance and physical performance of muscle in sarcopenia - 3

inc adipose tissue

inc inflammation

inc proteolysis accompanied by impaired regen. - dysfunction of satellite cells that are myogenic stem cells

what are myogenic stem cells

stem cells that make muscle cells

what happens to skeletal muscle in sarcopenia - 2

dec mass

functional impairment

what happens to mitochondria in skeletal muscle cells in sarcopenia - 6

lower number

mitochondrial dna mutations

morphological changes

inc apoptosis

impaired autophagy

impaired biogenesis

what is the impact of immune senescence/ immune dysfunction in elderly - 6

lower vaccination efficiency dec immune surveillance (esp women) dec resistance to infection inc cost of malignancies inc inflammation autoimmune activation

as we get older, is innate or adaptive immunity impacted?

bof so overall inc susceptibility of ncds

with inc age what happens to our b cells - 6

reduced amount of b cells made from bone marrow via hematopoeisis dec somatic hypermutation altered dna methylation inc pro inflammatory cytokine secretion inc autoantibody production red antibody affinity and neutralisation capacity

what are b cells

a type of white blood cell that make antibodies

impact of altered b cell function on disease prevalence?

inc risk of infections e.g. SARS-Cov-2, pneumonia, influenza inc onset of autoimmune disease e.g. systematic lupus erythematodes, rheumatoid arthritis, atherosclerosis

what are autoantibodies

antibodies that attack our own cells

main 3 impacts of ageing on immune senescence

impaired ability of immune system to respond to new pathogens/ antigens decreasing immunity to previously experienced pathogens/ antigens - dec in immunological memory low grade systemic inflammation aka inflammaging

impaired ability to respond to new pathogens examples - 2

SARS-CoV-2 fatality rate was 50% or more in those aged 65 or over West Nile virus - neuroinvasive disease (consequence of WN infection) in USA same trend

key driver of imapired ability to respond to new pathogen?

thymic involution

what is the thymic gland

produces and matures T cells esp in childhood, sits on top of heart, becomes involuted with age, stress, malnutrition

impact of involuted thymus - 3

less naive t cells produced into periphery dec ability to build immune response to new natural encounters dec ability to ammount immune response to new vaccine antigens

dec in immunological memory - what is this driven by - 7

inc dna damage constitutive activation of MAPK signalling pathway - sustains senescent phenotype loss of telomerase activity dec proliferative capacity upon activation of immune response inc cytokine prod and cytotoxicity AMPK activated by low ATP nutrient deprived phenotype - cells bad at using nutrients

dec in immunological memory - example

varicella zoster virus/ chicken pox - common when young as first encounter in older people, shingles - same virus. this is due to antibodies becoming less effective

what age is chickenpox most common in and why

1-7 younger - protected by mothers passed down immunity older - develops own immunity

low grade systemic inflammation occurs in which cells

all body cells e.g tnf, il-6, -8, etc

8 main contributing factors of inflammaging

excess ROS SASP immunosenesence autophagy proteostasis antigenic load genetics/epigenetics gut microbiota sex/gender

6 cell changes in sarcopenia

inc inflammation duh dysfunction of mitochondria inc ROS inc fat and fibrotic infiltration imbalance in protein turnover dysfunction of satellite cell