Ageing and Disease Flashcards
What does aging describe in biology
he result of a build-up of cellular and molecular damage over time that leads to a gradual decline in physical and mental abilities
Give some examples of diseases which are more predominant in aging populations
Cancer/ coronary heart disease/ dementia (Alzheimer’s is a type of dementia)
What is progeroid syndrome ?
A genetic disorder which is characterised through features mimicking physiological aging.
What is apoptosis?
programmed cell death - required to prevent cancer
What is longevity?
How long an organism lives for
What is senescene?
time-related deterioration
What is semelparity?
Group of organism which live up until they reproduce
Give some hallmarks of ageing.
Cellular senescence /mitochondrial dysfunction/ epigenetic alterations/ genomic instability / stem cell exhaustion …
What is genome integrity?
The ability to maintain the genome or all its DNA in a cell during cell division
What are some mechanisms used by cells to prevent DNA damage?
DNA REPAIR - // SCANNING FOR DNA DAMAGE-
What is the relationship between insulin signalling and longevity ?
calorific restriction promotes longevity (and increases insulin sensitibity)// mutants which partially block insulin signalling promote longevity
What is the role of animal models in investigating age?
Using a worm as a model the A.C. elegan mutation was found to double life expectancy
What is the role of the P53(“guardian of the genome”)?
A tumour repressing gene which activates apoptosis / senesce and DNA repair in response to DNA damage/ telomere dysfunction/ oncogene activation
What is the role of telomerase?
A reverse transcriptase which grows telomers (end units of a gene which are not often replicated and are therefore lost)
What is cellular senescene?
a tumour repressor which prevents the accumulation of excess cells by stopping cell division
What is the biological function of amyloid precursor protein(APP)?
To bind other proteins on the surface of cells or help other cells attach to one another//
What is proteolytic processing?
the cleavage of specific peptide bonds within a protein precursor changing the conformation of the protein
What proteolytic processes amyloid precursor protein?
APP is cleaved by Beta and gamma secretase, with beta gamma secretase being harmful as it cleaves the peptide at length 40-42, this creates aggregation and therefore cell death and dementia
What is the association between Amyloid precursor protein gene variants and familial forms of Alzheimer’s disease?
Different enzymes cleave the APP at different lengths, gamma secretase cleaves the peptide at length 40-42 amino acids, this is harmful, creating aggregation, cell death and therefore dementia
What is proteostasis?
The process by which cells maintain the balance of functional proteins (protein homeostasis )
Give examples of diseases which are associated with protein folding issues?
ALZHEIMER’S -> formation of amyloid plaques and neurofibrillary tangles // PARKINSONS-> lewy bodies are formed from x -synuclein
What are the 3 main types of proliferation of cells ?
Mitotic cells (continuously dividing~)// post-mitotic or quiescent (low or no division can e stimulate) // fixed post mitotic (no division under a stimulus)
What are the two types of late onset alzhiers disease?
- FAMILIAL - autosomal dominant, involves the APP and PSEN1 // 2. SPORADIC -> general population
What is the role of proto-oncogenes?
cell proliferation
What is the role of tumour repressor gene?
prevents cell proliferation, controlling cell growth
What is the difference between a mutagen and a carcinogen?
Mutagen binds to DNA and creates changes but carcinogens do not bind to DNA but are associated with cancer
What are the 3 basic stages of cancer development?
- INITATION- first mutation // 2. PROMOTION creation of the correct environment around the tumour // 3.PROGRESSION - cells proliferate
What is the difference between germline and somatic mutations ?
germline are heritable but germline are not
What processes can convert proto-oncogenes into oncogenes ?
- POINT MUTATION- deletion or point mutation in the coding sequence forming hyperactive protein // 2. GENE AMPLIFICATION- normal protein is produced just in large quantities // 3. CHROMSOMAL REARRANGMENT - the breaking and re-joining of protein’s forming overproducing proteins
What are some category’s of oncogenes?
GROWTH FACTOR -induces cell proliferation// RECEPTOR TYROSINE KINASES- transduce signalling for cell proliferation // SIGNAL-TRANSDUCTING PROTEINS- involved in signalling // TRANSCRIPTION FACTORS- regulates transcription of genes which induce proliferation
What are the two main categories of cancer and what is there characteristics in the context of breast cancer ?
- SPORADIC - no family history / older individuals / one tumour present / one breast (unilateral)// 2. FAMILAL - involves a gene - BRAC1/ younger individuals / multiple tumours present/ both breasts (bilateral)
What is the role of Rb?
Within G1 Rb becomes phosphorylates, realising E2F ( a transcription factor which stimulates the production of genes and proteins
Briefly outline the pathway of a normal cell cycle in response to DNA damage
- DNA damage is identified// 2. Protein kinase is released/ 3. P53 is activated via phosphorylation // 4. transcription produces a protein which inhibits the cell cycle therefore DNA damage is not replicated
Briefly outline the cell cycle in response to DNA damage in the absence of P53.
- DNA damage is identified// 2. Protein kinase is released/ 3. P53 is not activated due to mutation// 4. protein inhibiting cell cycle is not transcribed therefore not present therefore there is cell division of cell containing DNA damage
Outline some hallmarks of cancer.
Sustaining proliferative signalling / resisting cell death/ inducing angiogenesis/ enable replicative immortality / evade growth suppressor / activate invasion and metastis
How can breast cancer be treated?
surgery - biopsy// radiation therapy// chemotherapy// gene therapy
How do cancer cells cope with the increased demand of ATP?
amplify the number of glucose transporters , increasing glucose in cell used for ATP production via glycolysis // uses anaerobic glycolysis, faster than aerobic making more ATP
What occurs if the tumour repressor is inactive within cancer cells ?
cellular proliferation is unchecked and cellular defence mechanisms (apoptosis) no longer function meaning cells containing DNA damage are proliferated
What is the role of telomerase? Why is this beneficial to cancer cells?
maintain telomere length (during cell divisions telomeres can be lost, overtime this creates cell senesce and the cell stops dividing.)// cancer cells reactive telomerase to ensure division constantly occurs
Briefly outline the process of anagenesis .
- Primary tumour releases angiogenic signals // 2. Enzymes break down extracellular matrix of endothelial cells of blood vessel// 3. cell migrate into blood and proliferate // 4. enzymes break down intracellular endothelial cells, cancer cells migrate out of the blood and form a secondary tumour in a different location of the body
What is the theory behind tamoxifen being used to treat cancer?
Tamoxifen competes with oestrogen to bind to the receptor, when tamoxifen binds to the receptor there is no shape change of the receptor therefore the receptor cannot bind to co-activators and crate a response of cell proliferation
How can herceptin be used as a breast cancer treatment?
Herceptin attaches to HER2 receptor, stopping HER2 receptors from signalling to the cell to grow
What does anastrozole do?
Now used as a treatment for breast cancer/ blocks oestrogen production, as oestrogen is associated with cell proliferation it help control cell growth
What is oesteoprosis and oesteopenia?
Loss of bone density// oesteoprosis = 1-2.5SD below mean peak bone mass // oesteopenia = bone mass reduces 2.5 SD below mean
What are the two main cells involved in the remodelling of bones?
osteoblasts = building up bone// osteoclasts = breaking down
What is wolff’s law?
Physical activity stimulates bone remodelling, with bones being built in response to pressures
How does calcium and vitamin D affect bone density?
vitamin D is involved in the absorption of calcium, calcium is a key component in the inorganic portion of the matrix, providing flexibility
What are some hormones associated with osteoporosis?
PTH (parathroid hormone) / Calcitonin= regulate calcium // Glucocorticoids - increases bone reabsorption
What is osteoarthritis ?
a problem with bones at a joint // catlidge thins and losses water reducing flexibility and free movement of bones
What is sarcopenia?
loss of skeletal muscle mass, reducing the number and size of muscle fibres
What are some prevention methods for sarcopenia/ osteoarthritis/ osteopenia/ osteoporosis?
exercise (high magnitude targets bones mass)// nutrient intake (specifically focusing on calcium, vit D and lean protein.)
What is an emerging disease?
A disease which is increasing in the number of individuals infected within an area
What the main categories of emerging disease?
NEWLY EMERGING// RE-ERMERGING // DELIBERATLY (bioterrorism~) // ACCIDENTAL
What are some risk factors of emerging diseases?
Human (population growth// human travel// hunting…)// Ecological (climate events / El Nino South osscilation)
What are some factors which allowed West Nile Virus to get more established?
NEW YORK 1999
- dry spring
- reduction in predators
mosquito to bird transmission allowed birds to act as a revivor
- human travel transported the infected mosquito (the vector) to new York via aircraft
- climate change, warmer climate allowed virus to survive and thrive
Why do some CV diseases lead to other diseases?
Directly effects all somatic cells and organs through changing blood flow therefore altering oxygen and nutrient avalibility
What are some theories associated with aging and diseases?
WEAR AND TEAR// CELLUALR - stem cell exhaustion// GENETIC MUTATION - increases with age// AUTOIMMUNE THEORY - aging is involved in the decline of the body’s immune system
What causes the skin to wrinkle?
Dermal layer thins/ less collagen is produced/ elastin fibres providing elasticity wear out // reduction in function of sweat glands forming dry skin
What is sinus arrhythmias and sinus bradycardia?
both describe an irregular heart rate // Arrhythmias = 10% faster // Bradycardia = slower than 60bpm
What are some treatments applied to heart failure?
NITRATES - dilate blood vessels// POSITIVE INOTROPIC- reduces heart rate but increases force of contractions// ACE INHIBITORS - reduces blood pressure through reducing water retention in kidneys
What are some treatments used for reducing blood pressure?
Beta blockers/ calcium channel blockers / lifestyle changes (diet and exercise)
What is calcification?
reduction in elastin and an increase in collagen(reducing flexibility and ability to adapt to blood pressure)
How does aging impact coronary arteries?
reduces blood flow, reducing O2 delivery to cardiac muscle altering power and rate of contractions resulting in angina (a pain)
What is metformin? Why is it used for in industry?
A hormone which regulates cardiac rhythm// can now be used as a treatment for Alzheimer’s/ ischaemia stroke and cancer
What factors increase Type II diabetes likelihood with age?
reduced exercise levels / obesity/ reduction in insulin sensitivity/ reduction in muscle mass/ weight gain/ insulin secretion level reduces
What is a hormone and how does it travel around the body?
A chemical signalling molecule, produced by organs, cells or glands which travel through the blood.
What are some differences with water soluble and lipid soluble hormones?
LIPID SOLUBLE(steroid ) - Hydrophobic //Circulate primary bound to plasma proteins//Intracellular receptors // Promotes or supress gene transcription//// WATER
SOLUBLE (hormones)- Hydrophilic //Circulate primary dissolved in plasma //Cell surface receptors on target cells //Act via secondary messenger system //Modify target proteins (e.g. opens a membrane channel)
Give some examples of functions of the endocrine system
Homeostasis
Electrolyte, water , nutrient balance in blood
Cellular metabolism
Glucose and mineral homeostasis
Growth and development
Reproduction
Blood pressure control
Response to a stress
Production of immune cells
Outline the structure and function of the endocrine system.
hypothalamus - regulates pituitary gland// pituitary gland -> 1. posterior = extension of hypothalamus 2. anterior = synthesises and secretes some peptide hormones// thyroid and adrenals - produces hormones, controlling metabolism// pancreases- produces hormones regulating blood sugar levels / testes- produces testosterone // ovaries - produces oestrogen //
Outline the organisation of the endocrine system
Made up of gland and organs which produce and control hormones.
How is hormone secretion regulated?
1.Hypothalamus releases either releasing or inhibiting hormones to the anterior pituitary// releasing hormones makes anti pituitary secrete hormones into blood creating a response// inhibiting hormones stops hormone secretion from the anterior pituitary changing the effect on the target tissue
Give an example of a negative feedback system in the endocrine system
HYPOTHALAMIC-PITUITARY-THYROID-AXIS= 1. thyroid realising hormones (TRH) are released from hypothalamus // 2. stimulating hormonal release from anterior pituitary/ 3. T3 and T4 are released from the thyroid // 4. creates negative feedback on the anterior pititary and hypothalamus
*aim = maintain a hormonal balance
Give an example of a positive feedback system within the endocrine system
OESTROGEN
1. before ovulation oestrogen levels increase to develop the follicle creating a positive feedback loop// 2. increases LH stimulating granulosa cells (converts androgens to oestrogen// 3. triggers ovulation further increasing oestrogen
*this feedback loop becomes negative when ovulation halts and oestrogen levels drop
Describe some endocrine changes of the menopause
A lack of oestrogen is produced due to the progressive loss of follicles and therefore granulosa cells , creating a negative feedback loop. To compensate pituitary increases FSH (follicle stimulating hormones)
Give some examples of the effect of aging on the endocrine system.
little direct effects / hormonal changes occur due to changes in liver and kidney hormonal secretion and metabolism // drugs taken to combat other illnesses associated with ging can reduce hormone levels// most hormone levels reduce // target cells may become less sensitive
Why is hormone replacement therapy beneficial for women going through the menopause?
contain either oestrogen , progesterone or both// oestrogen - protects the individual from some symptoms// progesterone - protects the individuals from endometrial hyperplasia(thickening of uterus lining) and cancer
What are some risks associated with HRT (hormone replacement therapy)?
small increase in risk of getting breast and ovarian cancer // increase cardiovascular diseases//
What are some alternate treatments for menopause?
PHARMACOLOGICAL - anti-depressants / vaginal cream/ anticonvulsants gabapentin(for hot flushes) // NON-PHARMALOGICAL- diet chances, increasing vit D promoting calcium uptake// HORMONE REPLACMENT THERAPHY - alter oestrogen and progesterone levels
What is somatopause ?
A progressive decline in growth hormone GH secretion with age , often due to reduction in secretion of growth hormone releasing hormone GHRH
What are some metabolic changes associated with aging?
Increased body fat/ reduced protein synthesis , reducing muscle mass// reduced bone mass// reduced immune functions
What two cells develop during each menstrual cycle and what is there effect on oestrogen levels?
Theca- cells produce androgen // granulosa- cells convert androgen into oestrogen - both increase oestrogen levels
After ovulation what does the ruptured follicle transform into and what is the role of these during fertilisation and no fertilsation?
AT FERTILSATIPON 1. Corpus luteum- produces oestrogen and progesterone maintaining early stages of pregnancy after fertilisation 2. placenta take over production of oestrogen later// NO FERTILSATION 1. corpus luteum degenerates and oestrogen and progesterone levels fall
Describe neural signalling.
Process of communication between neurones the nervous system and other parts of the body. Involving neurotransmitters an synapses as well as chemical and electrical signals// signals travel through axon-> synapse.
What are some hallmarks of Alzheimer’s in the moderate stage?
MACROSCOPIC
difficulty with daily tasks / inability to remember current and personal events / inability to perceive danger / confused speech / mood changes
MICROPSCOPIC
misfolding and aggregation of proteins creating more neurodegeneration /
What are some hallmarks of Alzheimer’s in the late stage?
MACROPSCOPIC
inability to recognize family members / inability to do daily activities/ reduced ability to communicate / loss of bladder control / difficulty swallowing
MICROSCOPIC
further misfolding and aggregation of proteins creating more neruodegregation
What are the two main microscopic hallmarks of Alzheimer’s ?
beta-amyloid plaque formation = dense deposit of beta amyloid plaque outside and around neurons (Extracellular)// neurofibrils tangles = hyperphosphorylated tau creates impaired axon function
What is the amyloid cascade hypothesis?
theory explaining the primary cause of Alzheimer’s// the accumulation of amyloid-beta peptides in the brain caused by Amyloid precursor protein cleaving amyloid - beta peptide at either AB40 and AB42, When AB42 is produced more aggregation occurs forming plaques
What is the issue with diagnosing Alzheimers?
brain scans cannot discriminate between brain injury and Alzheimer’s as beta amyloid plaques and tau depositions in neurofibrillary tangles are also associated with brain damage
What is the cholinergic hypothesis?
A hypothesis explaining a pathological causes of Alzheimer’s// individuals produce less Acytle CoA in the nucleus basil of meynert in basal forebrain therefore the post synaptic cleft is not activated and memory loss occurs
What are some biomarkers of cognitive function
- A-Beta accumulation can be identified through the presence of CP molecules//2. neural degeneration is identified by a lack of glucose
What are some molecular pathogenesis of Parkinson disease
mitochondrial dysfunction - reduces ATP available to neurones / inflammation / oxidative stress- modifies proteins meaning they can no longer carry out functions/ protein transfer
What are some treatments for Parkinson’s disease?
REPLACING DOPAMINE LEVELS (MonoAmine Oxydase inhibitors - increases dopamine at synapse// DEEP BRIAN STIMULATION- redues rigidity// TRANSPLANTS USING STEM CELLS
What are some hallmarks of Parkinson’s disease?
Loss of dopamine neurone in SNpc (substantial nigra pars compacta) therefore delpeting dopamine levels
