biological system Flashcards
aging is accompanied by a number of universal and anticipated changes to biological systems
cardiovascular, digestive, endocrine, immune, nervous, integumentary, musculo-skeletal, reproductive, respiratory, urinary
Cardiovascular
Thickening left ventricle wall resulting in larger, less efficient heart; reduced and irregular heartbeat; reduced elasticity of arteries
digestive
Weakened esophageal contractions;esophageal sphincter; reduced elasticity of stomach; increased vulnerability to lactose intolerance
endocrine
Reduced reproductive hormones, reduced thyroid hormone; insulin resistance
immune
Increased vulnerability to infection (produces less proteins); increased autoimmune responses (body attacks itself; ie arthritis); reduced responsiveness to vaccinations
Nervous
Reduced visual(eyes become more yellow)/auditory(loss of hearing)/tactile acuity; decreased olfactory and gustatory sensitivity; structural and functional changes to brain;
integumentary
Thinning of epidermis, dermis, subcutis, reduced elasticity of skin, reduced ability to filter UV radiation
musculo-skeletal
Reduced bone density, muscle mass, increased rigidity of ligaments, tendones; thinning of cartilage
reproductive
Menopause (decreased estrogen production); “andropause”; changes in sexual functioning
respiratory
Reduced peak air flow; reduced gas exchanges; increased breathlessness
urinary
Reduced kidney size, increased rigidity and decreased capacity of the bladder; urinary incontinence
With respect to structural changes to brain; research has demonstrated brain atrophy with age:
Decreases in volume of 0.2% per year after age 35 and 0.5% per year after age 60
Shrinkage of gryi and widening of sulci
Shrinkage of specific regions (vulnerable regions include: prefrontal cortex, hippocampus, cerebellum)
Age related structural changes to brain
Shrinkage of gyri (outward folds)
Widening of sulci (inward folds)
Shrinkage of prefrontal cortex
Shrinkage of hippocampus (memory)
Shrinkage of cerebellum
1)Dopamine
Associated with attention, memory, movement, reward/reinforcement
produced in substantia nigra and ventral tegmental area (VTA) in midbrain
Evidence suggests dopamine functionality decreases with age
Decreases across the dopamine system (ie:receptors, synthesis capacity, transporters) range from —-per decade between young adulthood and older adulthood
3.7-14%
Transporter on presynaptic cell takes back some dopamine that is not reuptaken
Synthesis of dopamine decreases the lease/remains stable
Largest decline in Transporters (reduction of 14%)
Reuptake of dopamine decreases
2)Serotonin
Associated with mood, feeding, sleep, sexual behavior
Produced in the raphe nuclei of brainstem
2 billion neurons in our brain associated with the use of serotonin
Evidence suggest serotonin functionality decreases with age
Decreases across the serotonin system range from —- per decade between young adulthood and older adulthood
1.5-7%
Despite structural and functional changes noted above, research has demonstrated ongoing —–of the brain in older adulthood
neuroplasticity
Neuroplasticity(brain plasticity);
examples include development of new neurons (in hippocampus,olfactory bulb) and neuronal connections/synapses
As we get older we are still able to create new synapses
theories proposed to explain biological aging
1)genetic theories of aging
2)telomere theory of aging
3)free radical theory of aging
genetic theory of aging
aging is determined by genes that influence longevity and disease
aging is observed by majority of species
Maximum life span for various species:
correlation between brain size and lifespan( bigger brain=higher life span)
Small correlation between body size and lifespan (bigger bodies have shorter life span)
High Metabolic rate tend to have shorter life spans (loose negative correlation)
Gompertz law:
human mortality rate doubles every 8 years
Suggesting genes play a role in our life span
Maximum life span for humans is 122 years, where max life span of chimpanzees is 37 years.
Given that these two species share 98% of their DNA, scientists have suggested that relatively small number of genes influence aging
Examples of genes that are associated with longevity:
1)apoliproprotein E (APOE) gene
2)Forkhead BOX O (FoxO) gene
Apolipoprotein E (APOE) gene:
located on chromosome 19; associated with lipid transport and repair of brain injury
Forkhead Box O (FoxO) gene:
located on chromosome 6; associated with apoptosis, autophagy, and tumor suppression
FoxO 3
Allele 3 (FoxO 3)appears to be associated with longer life span (more likely to be found in centenarians and supercentenarians)
Apoptosis (FoxO)
organized (systematic) cell damage (cells commit suicide)
Autophagy
utilizes intracellular materials, brakes them down, and recycle for use WITHIN the cell
Tumor suppression:
cancer (uncontrolled division of cells)
Examples of genes associated with disease
1)kidney and brain expressed protein (KIBRA) gene
2)Lipoprotein A (LPA) gene
3)SH2B adapter protein 3 (SH2B3)
——– of variance of longevity in humans is due to genes; as we get older, genes play more important role of influencing aging
25-30%
Gene wide association study (GWAS)
looks at whole genome and looks for variance of genes between people
Candidate genes study
looks at how a candidate genes functions in individuals in relation to aging
interventions to combat age-related diseases and reduced life span
1)gene therapy
gene therapy
replace bad DNA with good DNA through genetic engineering
We create DNA that has good allele and then transfer DNA to host
1st way of gene therapy
injecting DNA in bloodstream and absorbed by cells
2nd way
inject DNA in tissue and hope it replicates the good DNA
3rd way (most popular):
create good DNA and attach it to a virus, virus create beneficial DNA and enters cells of host (virus introduces good DNA into the host)
Telomere theory of aging:
aging is determined by telomeres and their impact on cellular division
Hayflick limit (telomere theory)
cells undergo a finite number of divisions; the number of possible divisions declines with age
Lung tissue of older adults could only divide 20 times
cellular senescence
Cells that no longer divide are in a state of arrest and adopt a new form called senescence-associated secretory phenotype (SASP)
The stopping of cellular division is associated with—–
telomeres
SASPS
remain active and secrete molecules that promote inflammation, alter structure of surrounding tissues, and stimulate growth of malignant cells
SASPs diffuse bad molecules into our tissues/cells
SASPS —– as we age
accumulate
Moreover, SASP- like cells are found in affected tissues of patients with age-related diseases (ie osteoarthritis, atherosclerosis, alzheimer’s)
where are telomeres located
non coding portion at the end of chromosomes; they protect the ends of chromosomes from DNA degradation and fusion with other chromosomal ends
telomeres are —— as we get older
decreasing in length
what can telomeres do?
Telomeres give us the opportunity to extend life span potentially
researchers are investigating interventions (telomere gene transfer) to combat telomere shortening
Free Radical theory of aging
aging is determined by reactive oxygen species which cause cumulative damage to cells
Reactive oxygen species (ROS)
chemically reactive oxygen-containing molecules (ie oxygen radicals)
where is ROS generated?
The majority of ROS are generated by mitochondria as byproducts of adenosine triphosphate (ATP) production: ATP is the main energy source of ells
what do ROS do?
ROS attack and damage cellular macromolecules including proteins (protein fragmentation)
lipids (“leaky” cellular membrane:transport across our membranes are affected and resulting in loss of beneficial molecules)
and DNA
With age, damaged cellular macromolecules accumulate due to
increased production of ROS, decreased efficiency of repair systems, or both
Accumulation of damaged cellular macromolecules by ROS ultimately leads to cell death
Interventions for ROS
With respect to caloric restriction as an intervention, research in varied species (ie fish, hamsters, rats, dogs) has demonstrated than a 20-40% decrease in caloric intake reduce the onset of age-related diseases (cancer, cardiovascular disease) and increase life span by 20-50%
Caloric restriction
When we reduce calories, metabolism slows down, we reduce the accumulation ROS, leads to less macromolecule damage (controversial method)
With respect to functional changes to the brain, research has demonstrated changes in neurotransmitter with age
Neurotransmitter: chemical that enables the transmission of nerve
impulses between neurons
receptor(binding site for neurotransmitters on receiving cell)
studies that have excluded participants with cardiovascular risk factors or Covert brain disease have failed to reproduce some of these findings
covert brain disease: disease that has not yet become apparent
studies have excluded participants with these conditions have shown little or no deterioration of gray matter
