Aging in the Nervous System: Manaye Flashcards
What is aging?
the process of becoming older, a process that is genetically determined and environmentally modulated
What is senescence?
the decline of fitness components of an individual with increasing age, owing to internal deterioration
What is gerontology?
the scientific study of biological, psychological, and sociological phenomena associated with old age and againt
What is geriatrics?
the branch of medicine that deals with the diagnosis and treatment of diseases and problems specific to the aged
What is biogerontology?
the study of biology of aging and longeveity
What is the life span like in the US?
its increased over the years
females (82) have a higher life expectancy than males (74)
-our hormones keep us young
What are factors responsible for the increasing human survivorship?
- improved housing, sanitation, antiseptics
- public health, hygiene, immunization
- antibiotics, improved medical practice, nutrition, health education
- recent biomedical breakthroughs
Compare the proportion of population aged 0-14 versus 65 and older from 1861-2050
aged 0-14 is decreasing over the years
-significant reduction of young people due to family planning, professional training, and population control
65 and older is increasing over the years
What is the ultimate physician goal?
-to improve understanding of the mechanisms of longevity which can be used to fight age-related diseases and disabilities to ensure a healthy, active, and independent life well into very old age
What is ageism?
- can be seen as a process of systemic stereotyping and discrimination against people because they are old
- old people are categorized as senile, rigid in thought and manner, old-fashioned in morality and skills
- ageism allows the younger generations to see older people as different from themselves; thus they subtly cease to identify with their elders as human beings
What is successful aging?
when individual ages chronologically same as other old person but elderly person is preventing pathologies by making lifestyle changes to improve health
- with successful aging, an individual is enhancing cognitive and emotional health by:
1. exercising avoiding exposure to pathogen, radiation, noise, stress
2. maintaining a happy lifestyle and their psychological well being - maintain physical function
- avoid disease
- maintain mental function
- enjoy life
- there is a heterogeneity of various values and functions
- many associated with physical inactivity
What is cell senescence and death?
- biological responses to a variety of stresses that results in persistent growth arrest of damaged or dysfunctional cells with a distinct morphological and biochemical phenotype.
- its beneficial early in life but may contribute to aging later on
What are some senescence inducers?
- telomere dysfunction
- chromatin perturbation induced apoptosis/necrosis- generation of ROS that cause oxidative deterioration of biological molecules
- DNA damage
- strong mitogenic signals: DNA damage caused by ROS (by product of oxidative phosphorylation)
What are some senescence phenotypes as a result of senescence inducers?
- growth arrest
- functional changes
- resistance to apoptosis
What are the ecological theories of aging?
external factors that causes mutation or damage to DNA
- UV irradiation
- background irradiation-mutation
- physical use
What is programmed aging theory?
- normal expression of genetic program that begins at conception
- biological clock in cells dictate life span; subject to enormous variation
- this theory focuses on genetic programming encoded in our DNA
- determined by physical fitness, hygiene, and nutrition
What is cellular aging theory?
- wear and tear: the difference is how you keep yourself healthy- due to emotional and physical stresses to which we subject our bodies (i.e.UV rays from the sun)
- free radicals
- oxygen free radicals generated cause
cumulative oxidative damage, resulting in structural degeneration, (apoptosis), functional decline, and age-related diseases
What is mitochondrial dysfunction and aging theory?
cause the end of our chromosomes (telomeres) to shorten
- we have increased oxidative stress with normal aging; as a result, the damage they cause exceed the ability to scavenge free radicals or repair their damage
a. ROS damage mitochondria, DNA, proteins, lipid???
b. SOD and catalase reduce oxidative stress
c. In alzheimer’s disease the brain is under pronounced oxidative stress, caused by beta amyloid precursors
- Because the mitochondria regulates: iron metabolism; heme metabolis; programmed cell death; cellular division and differentiation—all these things will be affected
What is aging of the central nervous system?
as we age we have significant reduction in white matter and speed of neurotransmission
ischemia due to plaque build up that caused a stroke
changes in the speed of neurotransmission (the passing of chemical and electrical signals from one brain cell to another) likely underlie these age-related changes in processing speed
What are the problems involved in differentiating normal again from disease-related changes?
-chronological and physiological changes do not always coincide with physiological appearance and health status This could be due to a variety of factors including:
- complex interactions between genetics and environment
- functional plasticity, adaptation
- neural degeneration- difference between normal aging and disease related aging–AKA the lady that’s obese versus her twin dying of Alzheimer’s disease
What are the biochemical changes in CNS aging?
decreased production of neurotransmitters
- serotonin
- dopamine
- norepinephrine
- GABA
- acetylcholine
- decrease in choline acetyltransferase activity
decreased production of growth factors
- BDNF: Brain-derived neurotrophic factor
- NGF: Nerve growth factor
essentially you have decreased synapses and NTs = decrease in transmission of electrical signals
Describe the multiplicity of changes in CNS aging.
A decrease in catecholamine synthetic enzyme
Serotonin
Dopamine
Norepinephrine
GABA
Other Neurotransmitters (choline acetyltransferase)
Describe the structural, morphological changes in normal aging.
-decreased brain mass
- brain loses 5-10 percent of its weight between the ages of 20 and 90
- sulci is enlarged
- ventricles are enlarged
- gyri size is decreased
What are the cellular histological changes associated with aging?
- corpora amylacea
- lipofuscin
- granulovacular degeneration
- Hirano bodies
- Melanin increases
- Lewy bodies
- Amyloid Angiopathy
- Glial Changes
What is corpora amylacea?
a mixture of lipids and proteins that accumulate as brown pigment in some neurons with age. This represents failure of neurons to eliminate the products of peroxidation-induced cell damage
What is lipofuscin?
appears as membrane bound aggregates of granular osmiophilic materials and pale homogenous droplet. Lipofuscin are found in various neuronal populations including cerebral cortex and hippocampus.
What is granulovacuolar degeneration?
these intracytoplasmic vacuoles which represent degenerative process are found in the hippocampal neurons
-it contains proteins such as ubiquitin, tau, tubulin, and neurofilament
What are Hirano bodies?
rod-shaped, crystal-like, and eosinophilic structures found primarily in the hippocampal pyramidal neurons
they are composed of microfilament proteins such as actin and tropomyosin
Describe melanin increases.
pigment found in neurons of the substantia nigra (SN) and locus coeruleus (LC)
What are Lewy bodies?
- are found in normal elderly individuals particularly in the SN , LC, hippocampus, and in the cortex
- are composed of a core of osmiophilic granular and filamentous halo of radially oriented filamentous materials and pale homogeneous droplets
What is Amyloid Angiopathy?
this represents extracellular deposition of Aβ peptides in the arteries and arterioles of the cerebral blood vessels located primarily in the cortex
What are glial changes?
- astrocytes and microglia are activated in aging; their number show modest increase
- oligodendrocytes develop swelling along their processes which possibly contain broken myelin sheath
What occurs in LC during aging?
there is cell loss
What are amyloid plaques and disease are they associated with?
- are spherical, multicellular lesions containing Aβ peptides surrounded by dystrophic neurites, activated microglia and reactive astrocytes
- amyloid plaques cause Alzheimer’s disease
neuritic plaques do contain a number of other proteins including APOE, lysosomal proteases, proteoglycans, heparin sulfate, and complement cascade
diffuse Aβ deposits are present in large number in normal aging brain
these are thread-like structure in the neuropil of the grey matter that contain PHF-tau protein
they are restricted to the entorhinal cortex, hippocampus, and amygdala
What are the functional changes in the aging brain?
- sensory perception may change
- postural reflexes become sluggish
- memory deficits may occur
- sleep patterns change
- mood alterations may occur
How does vision change with age?
presbyopia: loss of ability to accomodate, has 100% incidence rate, given a life span of at least 50 years
- pupil size decreases
- pupil may also react more slowly in response to darkness or bright light
- lens becomes yellowed, less flexible, and slightly cloudy (cataracts)
- eye muscles become less able to fully rotate the eye
What are hearing changes associated with aging and what are some causes?
presbycusis: hearing loss associated with aging
some causes:
- atherosclerotic damage to the especially fine microvasculature of the inner ear
- thickening of eardrum
- genetic predispositions: possible mutations in myosin isoforms unique to hair cells
What are some other sensory changes?
cutaneous senses:
- sensitivity to touch is decreased
- some develop an increased sensitivity to light touch because of thinner skin
proprioception
- require greater angular acceleration
- exaggerated sway
decreased sense of smell and taste
-number of taste buds decreases
-begins about age 40-50 in women and 50-60 in men
-if taste sensation is lost, salty and sweet tastes are lost first, with bitter and sour tastes lasting slightly longer
vestibular function
-loss of hair cells of cristae ampullaris
How does sleep change with normal aging?
decreased circadian rhythm
-sleepiness will occur at anytime
fragmented sleep
-frequent awakenings
increased time in stages 1 and 2
-more light sleep
decreased time in stages 3 and 4
-less restorative, deep sleep
Changes in sleep cycle: takes longer to fall asleep, total time spent sleeping is less than their younger years, awakenings throughout the night, increase in frequency of daytime naps
What are the age related emotional changes?
in older person, stress is thought to play a bigger role in triggering depression than in other groups
managing stress can affect one’s outlook on life
- not all stress is negative
- chronic stress takes a toll on the brain
What is Age-related Memory Impairment?
memory types that show some impairment with age:
- episodic (autobiographical)
- personally experienced events
- short term
Memory types that show little or no impairment with age:
- semantic (knowledge)
- concepts and general facts
- vocabulary and language
- procedural (learned skills)
- how to do things (telling time)
Shipley = standardized clinical vocabulary test
What is progeria?
an extremely rare genetic disorder wherein symptoms resembling aspects of aging are manifested at a very early age (premature aging symptoms)
it is a genetic condition that occurs as a new mutation and is rarely inherited, as patients usually do not live to reproduce
What is Werner’s syndrome?
also known as “adult progeria” and is a rare, autosomal recessive progeria syndrome and characterized by the appearance of premature aging
the median and mean ages of death are 47-48 and 54 years respectively
the main cause of death is cardiovascular disease or cancer
What is dementia?
general decline in memory and in at least one of the following cognitive abilities:
- ability to generate coherent speech or understand spoken or written language
- ability to recognize or identify object, assuming intact sensory function
- ability to execute motor activities, assuming intact motor abilities, sensory function and comprehension of the required task
- ability to think abstractly, make sound judgments, plan and carry out complex tasks
What are some dementia-related disorders?
- dementia with Lewy bodies
- alcohol related dementia
- frontotemporal dementia (Picks disease)- abnormal tau
- protein accumulation
- vascular dementia
- Huntington’s disease
- Alzheimer’s disease
What is pathological process of alzheimer’s disease?
Pathogenesis: induced glial activation and cell death
- Abnormal amyloid precursor protein (APP) - thought to self-associated under certain circumstances to form proteinaceous aggregates called amyloid plaques
- these plaques lead to a broad spectrum of neuropathologies and result in neurotoxicity (glial activation–>inflammatory cytokines) and neuronal cell death
- Brain of AD pt shows enlarged sulci
- Tau protein
