Exam 1 Flashcards
What does aging mean?
o Aging is the random change in the structure and function of molecules, cells, and organisms that is caused by the passage of time and by ones interaction with the environment. Aging increases the probability of death
What is the goal of aging research?
extend their health span with less morbidity onset and compressed morbidity is much later,
What is commonly seen among centenarians?
rarely obese o substantial smoking is rare o better at handling stress o history of bearing children after 35 o relatives who live long o children score low in neuroticism and high in extraversion
What is Hutchinson-Gilform Progeria Syndrome?
o Phenotype: early appearance of symptoms normally associated with aging such as a shortened lifespan, growth impairment, and cardiovascular problems.
o Caused by mutations in LMNA (Lamin A gene): Lamin A helps with nuclear stability and chromatin structure. Other problems with the gene lead to many other age related disease such as muscular dystrophy and cardiomyopathy
How do you identify consider genes?
Take single genes of yeast one by one and identify in the worm the ortholog with a similar function and code and see that if it extends lifespan. Then you go into mice then go into mice and see if it extends lifespan.
What are the 4 biomarkers of aging?
Predict the rate of aging (reveal exactly where the person is in his or her biological lifespan-better predictor than chronological age
Monitor aging, not disease
Testing without harming individual
Must be a marker that can be examined in other model organisms
What impacts our individual biological age?
o Genetics: Intrisnic Rate of Aging (70-80%) with the genotype or the genetic make-up of an organism
What is epigenetics
the study of changes in gene expression, without altering the DNA sequence
How is epigenetic accomplished?
- DNA and histone methylation: addition of a methyl group
2. Histone acetylation
What does DNA and histone methylation do?
➢ Methylation silence gene expression in 2 ways: impeding transcription factor binding or causes methyl-CpG- binding domain proteins to bind and recruit chromatin remodeling proteins to form heterochromatin
What does Histone acetylation do?
- the addition of an acetyl group to lysines giving more gene expression as it neutralizes the charge and loosens the histone complex. Can acetylate other proteins besides histones.
What is some evidence that epigenetic affects aging?
- aging is accompanied by changes in DNA methylation and histone modifications
- studies in model organisms have shown a causal relationship between chromatin modifiers and lifespan
What are the effects of normal again? and how can they be enhance?
o loss of subcutaneous fat o thinning dermis o loss of collagen fibers lose 30-50% of muscle mass between 30-80 can be lost by environment without affecting genes due to more UV exposure increasing breakdown rate of collagen and elastin as well as wrinkle, and sun spots
Cross sectional studies of aging are?
comparing a church group snapshot (average rate of change in a particular system) of average deaths to average americans indicating have the genes to live long but not the environment at single point in time
What are longitudinal studies?
collection of changes from the same person over time. show pattern of individual in population, genetic vs. environmental causes of death
What do mortality curves show?
graph representation of survival over time which estimates the rate of aging in a population
What are the four components of natural selection?
- Variation. Organisms (within populations) exhibit individual variation in appearance and behavior.
- Inheritance. Some traits are consistently passed on from parent to offspring. Such traits are heritable, whereas other traits are strongly influenced by environmental conditions and show weak heritability.
- High rate of population growth. Most populations have more offspring each year than local resources can support leading to a struggle for resources.
- Differential survival and reproduction. Individuals possessing traits well suited for the struggle for local resources will contribute more offspring to the next generation.
Most scientists of Darwin’s time believed that the soma (body) cells transmitted properties of heredity to the germ (sex) cells
What are the three foundations of evolutionary theories of longevity and aging?
- Separation between soma and germ cells
- Aging is nonadaptive
- Extrinsic rate of aging
What is the theory behind the separation between soma and germ cells?
led to the “Trade-off” hypothesis:
Somatic cells exist solely to support germ cells and their unction oto pass on genetic material and ensure reproduction
➢ once finished, no need for the soma, and aging and death will follow
What is the theory behind aging as being nonadaptive?
➢ Reformulated Theory: as soon as the trait becomes useless for an individual, natural selection no longer acts to either remove or maintain the trat: is a non-adaptive trait
What is the exception to the non-adaptive trait theory?
care given by grandmothers to children allowed their daughters to have more children, therefore, increasing the fitness for the species as grandmother and grandchild relationship separates our species from all others.
➢ long post-reproductive life span may have been selected for because of its benefits to reproductive success. The greater the age of the grandmother living with the family, the more grandchildren
older woman unable to reproduce via the extension of menopause hypothesis
questioning whether lived long enough to take care of children and have that fitness or if grandma lived longer because children took care
What is the theory behind the extrinsic rate of aging?
the force of natural selection declines with age despite the exception of the grandmother hypothesis. not one factor increasing probability of death but just because they were around longer they experienced more hazard.
What is longevity linked to?
• Longevity is closely linked to genes selected for survival to reproductive age- longevity has evolved
• the slow decline in physiological function (AGING) could not have arisen through natural selection
o Aging has not evolved
o does not mean genes are not involved in aging, just means that they were not subjected to forces of evolution for that purpose
only been living this long for 50 years so we havent evolved
What are the 2 theories of aging or the evolutionary account for age-related decline in biological function?
- antagonistic pleiotropy
2. disposable soma theory
What is antagonistic pleiotropy?
(active opposition)
(single gene more than one trait)
➢ genes conveying a benefit for fitness early in life will be selected even though they may be disadvantageous in later life
➢ example: calcification of bone during fetal and childhood development
highly regulated process
reproductive advantage: protection of internal organs, body stability
detrimental later in life; calcification of arteris (coronary artery disease and myocardial infarction)
cell senescence
What is the disposable soma theory?
o Predicts that an organism will optimize resources so that there is high fideility in the DNA of the gamete, with the leftover resources directed to maintenance of the soma. At some point during the post-reproductive period, extrinsic aging will cause an accident ot occur in the soma. The soma will not have the resources necessary to repair the function, and aging will ensue.
due to finite resources in all environments, the best use of resources is to give highest priority to the cells responsible for the continuation of the species: the germ line
➢ supporting cells (ex. soma) would need only enough resrouces to ensure their primary job supporting the germ line to reproduction
➢ soma can be disposed once reproduction has occurred.
What is cellular aging?
aging of an organism is characterized by a progressive decline in cellular maintenance, defense, and repair processes, resulting in the gradual loss of homeostasis and functionality of tissues and organs over time. Loss of cells then loss of tissues.
• Accumulation of damaged molecules, in our cells is a balance of damage and repair. When young less damage and lots of repair, vice versa when you are older due to the accumulation of damage
What are the major cellular processes implicated in cellular aging?
o Cell cycle and division- cell senescence, DNA damage, and telomere shortening
o Mitochndrial function- oxidative stress from creating energy and free radical production
o endoplasmic reticulum function- protein homeostasis, ER stress
What is the order of the cell cycle?
and what is the G0 phase?
G1 S G2 M
G0- “Quiescent state”-The cell has exited the cell cycle, but still active. Cells that are post-mitotic, or senescent stages.
What are CDKs?
cyclin dependent kinases and they function throughout the cell cycle and their activity changes during the different stages
What are cyclins?
they regulate cdk activity through direct binding.
➢ G cyclins: promotes passage through Start (Cyclin D)
➢ G1/S cyclins: Bind cdks at end of G1 and commit to DNA replication (Cyclin E)
➢ S-cyclins : Initiate DNA Replication (Cyclin A)
➢ M-cyclins: Triggers entry into Mitosis (Cyclin B)
What are CKI?
a CDK inhibitor protein that negatively regulates the cell cycle and it is p27 and p21
How does the progression of the cell cycle occur?
transcriptional regulation, cyclical proteolysis, and activity regulation
What are the three major checkpoints in the cell cycle to evaluate the process?
G2-M phase, 1/2way through M phase, and G1-S phase
how is the cell cycle regulated at the G1 phase?
cell cycle initiates when cell receives an extracellular signal from “mitogens”the activates cyclin, then cdk is activated by cdc25 phosphatase removing a phosphate from cdk, growth factors PDGF and EGF
How is the cell cycle regulated at the G1/S phase?
normal method which triggers DNA replication machinery
P53 is the gatekeeper of the genome and it is activated in stressful situations where proteins then phosphorylate p53 which accumulates in the cell. then p53 (transcription factor) binds to p21 promoter and p21 halts the cell cycle at this point.
What happens when the S phase is triggered?
origin firing is triggered, and it prevents further replication.
What is the regulation at the M phase?
1) up regulation of cyclin
2) activation of cdc25, which removes the inhibitory strain on cdk1
3)triggering mitosis
the activates cyclin, then cdk is activated by cdc25 phosphatase removing a phosphate from cdk
What is the regulation at the G2/M phase?
- DNA damage inactivates cdc25 so cdk is not activated and able to bind to cyclins
What is the metaphase to anaphase checkpoint regulation?
anaphase-promoting complex which when activated breaks down the m-cyclin, cdk and securin
with a ubiquitin ligase- which initiates proteasomal degradation, initiates sister-chromatid separation, degradation of securing- releasing cohesions. Leads to the degradation of securing which allows the sister chromatids to actually separate.
What is the G0 phase?
• G0 phase- allows cell to carry out physiological role without diverting energy to cell cycle.
What are the post-mitotic cells?
heart, muscle, brain
What are the mitotic cells?
gbroblasts, keratinocytes, lens cells, endothelial cells, lymphocytes, germ cells, stem cells- just need growth factors even I starving but they need some growth signals in order to enter into the growth cycle
What are the semi-mitotic cells?
liver cells, visual, hair, follicles. Can proliferate if there is the complete right conditions
