Aging 410 final
Findings that are incompatible with the mitochondrial theory of aging include: In some species, the correlation between ROS production level and longevity is positive Antioxidant supplementation can have negative health-related outcomes In some species, administration of antioxidants can have deleterious effects on lifespan Some long-lived mutants and species have both high ROS production levels and high levels of oxidative damage Antioxidant supplementation can suppress positive exercise-induced adaptations.
In some species, the correlation between ROS production level and longevity is positive In some species, administration of antioxidants can have deleterious effects on lifespan Some long-lived mutants and species have both high ROS production levels and high levels of oxidative damage
The American Federation for Aging Research has a somewhat different set of key criteria than Mather et al. (2011) and that must be met in order for a biomarker of aging to be valid. It must predict a person's cognitive function in an age-related way. It must predict a person's physical function in an age-related way. It must predict the future onset of age-related conditions and diseases. Its prediction of the future onset of age-related conditions and diseases must be independent of chronological age
It must predict a person's cognitive function in an age-related way. It must predict a person's physical function in an age-related way. It must predict the future onset of age-related conditions and diseases. Its prediction of the future onset of age-related conditions and diseases must be independent of chronological age
At the time that Charles Darwin published his theory of evolution, most people in England did not believe his ideas because: most people in England at that time rejected the ideas of Malthus about the relationship between population size and availability of resources. the concepts of "heritability" and "genetics" hinted at by Darwin had not yet been demonstrated. acceptance of the Biblical explanation(s) of the origin of life on Earth the idea of "programmed death" as the cause of aging was too ingrained. the idea of a "natural selection" was not actually presented in Darwin's original work.
acceptance of the Biblical explanation(s) of the origin of life on Earth
If it is possible to slow human aging using an "anti-aging" intervention (given the KN 410 definition of aging), it would be reasonable to expect that the intervention would: affect structure and function at some level delay the onset of age-related disease slow the progression of age-related disease increase healthspan increase lifespan
affect structure and function at some level delay the onset of age-related disease slow the progression of age-related disease increase healthspan increase lifespan
From the perspective of Darwinian evolution, the concept of programmed aging and programmed death does not make sense and is rejected because: aging reduces the fitness of the individual aging is not adaptive genes that would cause aging of an individual decrease the fitness of an individual natural selection favors adaptive traits genes that cause a non-adaptive trait such as aging would not be selected
aging reduces the fitness of the individual aging is not adaptive genes that would cause aging of an individual decrease the fitness of an individual natural selection favors adaptive traits genes that cause a non-adaptive trait such as aging would not be selected
Longevity genes, also called longevity assurance genes: are variations in some genes that confer longer life to those that have the genes compared to those who have other versions of the gene are variations in some genes that may confer better health to those that have the genes compared to those who have other versions of the gene have been identified in animal models such as roundworms and fruitflies and these genes have counterparts in mammals are the "opposite" of genes that increase the risk of diseases such as cancer, heart disease and Alzheimer's disease. are heritable, i.e., passed from parents to offspring.
are variations in some genes that confer longer life to those that have the genes compared to those who have other versions of the gene are variations in some genes that may confer better health to those that have the genes compared to those who have other versions of the gene have been identified in animal models such as roundworms and fruitflies and these genes have counterparts in mammals are the "opposite" of genes that increase the risk of diseases such as cancer, heart disease and Alzheimer's disease. are heritable, i.e., passed from parents to offspring.
The relatively limited published data regarding caloric restriction by humans suggests that caloric restriction by humans is feasible the sex-dependency of the effects of caloric restriction is an important consideration caloric restriction beneficially affects some potential longevity variables that are also observed in calorically restricted animals caloric restriction improves risk factors for some age-related pathologies maintaining a long-term large caloric restriction, even by motivated volunteers, may be difficult
caloric restriction by humans is feasible caloric restriction beneficially affects some potential longevity variables that are also observed in calorically restricted animals caloric restriction improves risk factors for some age-related pathologies maintaining a long-term large caloric restriction, even by motivated volunteers, may be difficult
A gene mutation can arise spontaneously may be induced may cause a loss-of-function or gain-of-function may cause harmful or beneficial effects may not cause any effect
can arise spontaneously may be induced may cause a loss-of-function or gain-of-function may cause harmful or beneficial effects may not cause any effect
The underlying premises of Harmon's Free Radical Theory of Aging include: cellular metabolism generates free radicals free radicals generated by cellular metabolism can damage mitochondrial DNA (mtDNA) mtDNA damage can lead to cell and tissue dysfunction aging may be caused by cellular damage caused by free radicals that are generated by cellular metabolism
cellular metabolism generates free radicals aging may be caused by cellular damage caused by free radicals that are generated by cellular metabolism
Chondrocytes are sensitive to forces and this sensitivity allows them to alter/modify the forces to which they are subjected. This can occur because: chondrocytic response to force can cause it to alter the composition (structure) of the extracellular matrix altered composition (structure) of the extracellular matrix can affect the function of the extracellular matrix the functional changes to the extracellular matrix can include changes to its stiffness the structural changes to the matrix can include changes to the quantity of collagen and proteoglycan the functional changes extracellular matrix can affect the forces to which chondrocytes are subjected
chondrocytic response to force can cause it to alter the composition (structure) of the extracellular matrix altered composition (structure) of the extracellular matrix can affect the function of the extracellular matrix the functional changes to the extracellular matrix can include changes to its stiffness the structural changes to the matrix can include changes to the quantity of collagen and proteoglycan the functional changes extracellular matrix can affect the forces to which chondrocytes are subjected
Senescent cells may contribute to aging if they develop a secretory phenotype that contributes to an inflammatory state contributes to cell growth, division and, invasion and destruction to surrounding tissue secretes enzymes that break down matrix proteins changes the structure of tissues changes the function of tissues
contributes to an inflammatory state secretes enzymes that break down matrix proteins changes the structure of tissues changes the function of tissues
Age-related changes that occur to chondrocytes include: decreased proliferation increased apoptosis increased senescence decreased sensitivity to growth factors decreased sensitivity to loads(forces) and deformation
decreased proliferation increased apoptosis increased senescence decreased sensitivity to growth factors decreased sensitivity to loads(forces) and deformation
Which of the following are objectives of the discipline of gerontology? elimination of premature disability determination of the mechanisms that increase susceptibility to acute and chronic diseases elimination of premature death characterization of variables that are associated with longevity characterization of the mechanisms that regulate aging
elimination of premature disability elimination of premature death characterization of the mechanisms that regulate aging
According to the Antagonistic Pleiotropy Theory, aging occurs because: mutations can accumulate continuously following reproductive maturity genes for adaptive traits that are expressed early in an organism's life may associated with maladaptive traits when expressed later in the organism's life the energetic costs of maintaining the genetic fidelity of germ cells exceeds that of maintaining the genetic fidelity of somatic cells. maladaptive genes that are expressed after reproductive maturity are not efficiently eliminated by natural selection maladaptive and adaptive late acting genes that are expressed after reproductive maturity are not efficiently eliminated by natural selection
genes for adaptive traits that are expressed early in an organism's life may associated with maladaptive traits when expressed later in the organism's life
The variables that have been shown to influence the effects of a calorically restricted diet include: genotype phenotype sex genus age at the time the caloric restriction was initiated
genotype sex genus age at the time the caloric restriction was initiated
Which of the following are true? germ cells have greater capacity for DNA maintenance than somatic cells long-lived organisms are more efficient at somatic cell maintenance than short-lived organisms DNA repair occurs faster and to a greater extent in a horse compared to a mouse there is an indirect (i.e., negative) relationship between DNA repair capacity and longevity there is a direct (i.e., positive) relationship between DNA repair capacity and longevity.
germ cells have greater capacity for DNA maintenance than somatic cells long-lived organisms are more efficient at somatic cell maintenance than short-lived organisms DNA repair occurs faster and to a greater extent in a horse compared to a mouse there is a direct (i.e., positive) relationship between DNA repair capacity and longevity.
Generally, non-human primates subjected to long-term caloric restriction: have increased healthspan have increased lifespan have decreased incidence of chronic disease have decreased incidence of serious infectious disease have similar reproduction patterns as non-calorically restricted animals
have increased healthspan have decreased incidence of chronic disease
Based on the mitochondrial theory of aging, decreased levels of superoxide dismutase found in the mitochondria of humans with end-stage osteoarthritis may contribute to the progression of the disease because: the proliferative capacity of chondrocytes would decrease telomere length of nuclear DNA would be expected to decrease increased damage to mitochondrial DNA would be expected cellular ability to synthesize structural proteins would be expected to decrease the surface of the articular cartilage would be expected to degrade
increased damage to mitochondrial DNA would be expected
Biological age: is a function of within-individual differences and between- individual differences in the onset of aging and the rate of aging of cells, tissues and organs. underlies the increasingly large between-individual differences that arise as a function of chronological age is an estimate of anatomical differences of an individual compared to her/his peers. can be positively influenced by diagnosed and undiagnosed disease can be negatively influenced by diagnosed and undiagnosed disease
is a function of within-individual differences and between- individual differences in the onset of aging and the rate of aging of cells, tissues and organs. underlies the increasingly large between-individual differences that arise as a function of chronological age can be negatively influenced by diagnosed and undiagnosed disease
A biomarker: is an objective and quantitative measure of structure is an objective and quantitative measure of function is an objective and quantitative measure of processes may be used to evaluate health status may be used to evaluate response(s) to intervention(s)
is an objective and quantitative measure of structure is an objective and quantitative measure of function is an objective and quantitative measure of processes may be used to evaluate health status may be used to evaluate response(s) to intervention(s)
The stiffness of a tissue or material: limits its elasticity can be measured when the tissue or material is subjected to any type of load is determined from a load-deformation curve quantifies the force required to cause a specific deformation represents the resistance to deformation in units of force per deformation
is determined from a load-deformation curve represents the resistance to deformation in units of force per deformation
Depending on the animal, the above shared characteristic may be caused by: low levels of circulating growth hormone misfolded growth hormone secreted by the pituitary gland decreased expression of the IGF-1 binding protein low levels of circulating IGF-1 problems affecting the function of growth hormone receptors or IGF-1 receptors
low levels of circulating growth hormone low levels of circulating IGF-1 problems affecting the function of growth hormone receptors or IGF-1 receptors
An ideal hallmark of aging meets which of the following criteria: it becomes evident with NORMAL aging and some disease states making the hallmark worse (i.e., aggravating the hallmark) speeds up normal aging measured values of the hallmark do not change when assessed repeatedly improving the hallmark (i.e., ameliorating the hallmark) slows down normal aging improving the hallmark improves healthspan
making the hallmark worse (i.e., aggravating the hallmark) speeds up normal aging improving the hallmark (i.e., ameliorating the hallmark) slows down normal aging improving the hallmark improves healthspan
Findings that support the mitochondrial theory of aging include: oxidative damage increases with age reducing oxidative stress reduces oxidative damage mitochondrial function gradually decreases during aging inhibition of mitochondrial function can enhance ROS production several age-dependent diseases are associated with significant increases in oxidative stress.
oxidative damage increases with age mitochondrial function gradually decreases during aging inhibition of mitochondrial function can enhance ROS production several age-dependent diseases are associated with significant increases in oxidative stress.
The results of Borras et al. (2003) show that estrogen is protective against oxidative damage to the mitochondrial DNA of rats by demonstrating: higher antioxidant production in the mitochondria of female rats compared to male rats higher mitochondrial DNA damage in male rats than female rats similar levels of antioxidant production by the mitochondria of female and male rats after ovariectomy similar levels of oxidant production by the mitochondria of female and male rats after ovariectomy significantly decreased oxidant production by the mitochondria of ovariectomized females after estrogen replacement. significantly increased anti-oxidant production in the mitochondria of ovariectomized females after estrogen replacement.
similar levels of antioxidant production by the mitochondria of female and male rats after ovariectomy similar levels of oxidant production by the mitochondria of female and male rats after ovariectomy significantly decreased oxidant production by the mitochondria of ovariectomized females after estrogen replacement. significantly increased anti-oxidant production in the mitochondria of ovariectomized females after estrogen replacement.
Cell senescence qualifies as a hallmark of aging because senescent cells accumulate during normal aging in all tissues even though senescent cells may not undergo apoptosis the accumulation of senescent cells accelerates aging decreasing the number of senescent cells slows aging decreasing the number of senescent cells increases healthy lifespan
the accumulation of senescent cells accelerates aging decreasing the number of senescent cells slows aging decreasing the number of senescent cells increases healthy lifespan
The loss of estrogen can accelerate age-related bone mass loss because: the loss of estrogen increases the amount of RANKL that is secreted by bone cells the loss of estrogen increases osteoclastogenesis the loss of estrogen decreases osteoclast apoptosis the loss of estrogen will increase the number of senescent osteocytes that become secretory the loss of estrogen will increase the blood levels of calcium
the loss of estrogen increases the amount of RANKL that is secreted by bone cells the loss of estrogen increases osteoclastogenesis the loss of estrogen decreases osteoclast apoptosis
The between-species similarities with respect to the effects of caloric restriction can be explained by the underlying mechanisms having evolved early in the history of life metabolic rate the underlying mechanisms having been conserved male-female differences environmental similarities
the underlying mechanisms having evolved early in the history of life the underlying mechanisms having been conserved
According to the AFAR document on the topic of Biomarkers of Aging, what is a potentially fruitful area in the search for biomarkers of aging?
Accumulation of senescent cells
Define aging.
Aging is a series of cumulative, progressive, intrinsic and deleterious functional and structural changes that (usually become measurable at or around the end of development), i.e., reproductive maturity and that (decrease the ability of the organism to respond to stressors) and (increase the probability of death).
What purposes could be served by an accurate biomarker of aging"?
An accurate biomarker of aging could be used to (1) monitor/evaluate interventions that have been designed to (2) delay the onset and/or slow the progression of aging.
Human lifespan that exceeds 100 years is considered "extreme" and/or "exceptional". Why is this so?
Because survival for men and women past age 100 is, statistically, rare
What is the definition of "biological age"?
Biological age is an (1) estimate of the functional status of an individual (2) compared to her/his peers
What would be a potential and reasonable explanation if the above-referenced hypothesis was found to be experimentally supported?
relaxed selection
the average number of years of life that is expected at the time of her/his birth is referred to as
Life expectancy
What are the variables that are used to characterize osteoporosis?
bone mass; bone architecture
Caloric restriction refers to a. reducing caloric intake b. reducing specific nutrients c. decreasing caloric intake while maintaining essential nutrient requirements d. limiting meals to specified periods of time e. decreasing caloric intake and selected non-essential nutrients
c. decreasing caloric intake while maintaining essential nutrient requirements
What are two events that typically happen to a cell after repeated cell division causes the cell to reach its Hayflick limit?
The cell becomes senescent and then undergoes apoptosis.
In contrast to caloric restriction, fasting diets focus on the frequency of fasting and may or may not involve a restriction of caloric intake during non-fasting times. List four varieties of fasting diets
Time-restricted feeding, alternate day fasting, 5:2 eating, periodic fasting
What is a pleiotropic gene?
a gene that may contribute to multiple phenotypic traits,
Darwin's concept of natural selection was that of a mechanism, or process, that led to between-organism differences in phenotypes that are also called _____________ which, in turn, increased the organism's ability to ________________. This is referred to as the organism having _____________ __________________
adaptations; reproduce; increased fitness
According to the Mutation Accumulation Theory, aging occurs because: a. mutations accumulate throughout an organism's lifespan b. late acting maladaptive genes that are expressed during development are not efficiently eliminated by natural selection c. late acting maladaptive genes that are expressed after reproductive maturity are not efficiently eliminated by natural selection d. genes for adaptive traits that are expressed early in life may be associated with maladaptive traits that become evident later in organism's life e. unrepaired somatic damage accumulates because there is an energetic trade-off between maintaining the genetic fidelity of germ cells and repairing and maintaining somatic cells.
c. late acting maladaptive genes that are expressed after reproductive maturity are not efficiently eliminated by natural selection
According to the Disposable Soma Theory, aging occurs because: a. what is known as the selection shadow reduces the ability of natural selection to eliminate genes b. genes for adaptive traits that are expressed late in an organism's life are not eliminated by natural selection. c. the accumulation of unrepaired damage that results from an evolutionary trade-off that favors investing energy into maintaining the genes of germ cells instead of maintaining the genes of somatic cells. d. maladaptive genes that are expressed prior to reproductive maturity are more likely to be eliminated by natural selection e. the accumulation of unrepaired damage that arise due to an evolutionary trade-off that favors maintaining the genes of germ cells instead of maintaining the genes of post-mitotic cells.
c. the accumulation of unrepaired damage that results from an evolutionary trade-off that favors investing energy into maintaining the genes of germ cells instead of maintaining the genes of somatic cells.
Research of the causes of human aging relies to a large extent on using animal models. The common patterns of aging, genetics and molecular signaling pathways between these animals and humans can be attributed to all of them being evolutionarily related to a
common ancestor.
What are the effects of reduced lifetime exposure of IIS on human longevity? a) shorter stature (height) b) shorter stature (height) and increased longevity c) shorter stature (height), increased longevity and a trend toward increased disability. d) shorter stature (height) and increased longevity but only for women. e) shorter stature (height), increased longevity and a trend toward increased disability but only for women.
d) shorter stature (height) and increased longevity but only for women.
The definition of biological evolution includes mention of: a. inherited traits b. changes in inherited traits c. changes in inherited traits of individuals d. changes in inherited traits of a population that occur from one generation to the next e. selective changes in the inherited traits of a population that occur from one generation to the next that preserve only those traits that maximize the likelihood of survival and reproduction.
d. changes in inherited traits of a population that occur from one generation to the next
Using data from a life table for a group of animals treated with an "anti-aging" intervention, one could determine if the anti-aging claims were valid by using the data from a life table of the same type of animals that had not been treated with the intervention. The determination would be made by: a. determining the ratio of the maximum lifespan to the median lifespan for each group, and then statistically comparing the ratios of the two groups. b. computing the slope of the line of identity for the age-specific mortality data for each group and then statistically comparing the slopes of the two groups. c. determining the slope of the line for each group between the age at which 10% of the population has died and the maximum lifespan of the population, and then statistically comparing the slopes of the two groups d. determining the slopes of the line of the log-transformed age-specific mortality data for each group and then statistically comparing the slopes of the two groups. e. determining the slope of the line for each group between the age at which 10 percent of the population has died and the median lifespan of the population, and then statistically comparing the slopes of the two groups.
d. determining the slopes of the line of the log-transformed age-specific mortality data for each group and then statistically comparing the slopes of the two groups.
In rodents, unless the extent of the caloric restriction is so large as to cause malnutrition, as the size of caloric restriction increases, i.e., as the caloric intake decreases: a. healthspan remains relatively constant b. healthspan increases proportionally c. median lifespan remains relatively constant d. median lifespan increases proportionally e. median lifespan and healthspan increase proportionally
e. median lifespan and healthspan increase proportionally
The associations between the prevalence of mobility disability and both annual household income and education level are: a. statistically significant b. not statistically significant c. not statistically significant but meaningful d. positive (direct) e. negative (indirect)
e. negative (indirect)
Although it has been hypothesized that caloric restriction will not increase human maximum lifespan an experiment to directly test the hypothesis in humans has not been conducted and is not likely to be conducted. However, a proposed method to test the hypothesis is to determine if caloric restriction causes a significant between-group difference where the groups are: a. short-lived mammals vs. long-lived mammals b. short-lived saltwater fish vs. long-lived saltwater fish c. short-lived non-flying insects vs. long-lived flying insects d. short-lived non-flying birds vs. long-lived flying birds e. short-lived non-flying birds vs. short-lived flying birds
e. short-lived non-flying birds vs. short-lived flying birds
What is the name of the ability of a tissue or material to be deformed when subjected to load and to return to its original dimensions when the load is removed?
elasticity
A higher than normal rate of, or increased tendency of gene mutations due to inaccurate copying is a hallmark of aging called __________________________ _______________________
genomic stability
The age-related progressive decline in immune system function is called
immunosenescence.
The average number of years of life remaining for a human at a specific age is referred to her/hi
life expectancy
The specific metabolic rate of mammals is indirectly and non-linearly related to the longevity of the animal. Based on the Rate of Living Hypothesis, animals that have faster metabolic rates have shorter lifespans than animals that have slower metabolic rates. In this context, why do Little Brown Bats discredit the Rate of Living Hypothesis?
little brown bats live much longer that similar sized animals
The long-lived dwarf mice discussed in class (i.e., Snell, Ames, Laron and IGF-1R knockdown mice) share a common characteristic that is the cause of their longevity. What is this characteristic
lower, lifelong, levels of IGf-1
The age at which half of a population has died and half of the same population remains alive is referred to as
median lifespan
The maximum isometric force of skeletal muscle fibers of older adults is smaller than that of young adults. The muscle fibers of older adults have smaller cross sectional areas than those of young adults. What is the name of the variable that is computed using this information and that leads to the explanation that the mechanism(s) of age- related decrease of maximum isometric force must reside at the level of the crossbridges?
muscle quality/specific force/specific tension
Cell death that is due to acute injury and that causes the contents of the cell to be released into its surrounding matrix is called _________. In contrast, programmed cell death, is called _____________
necrosis; apoptosis
Why can relatively small increases in bone mineral density have a large effect on the strength of bone?
new bone is deposited where it will have the largest biomechanics benefit
Has the relationship between oxidative stress/damage in articular cartilage and osteoarthritis been demonstrated to be a causal relationship?
no
After the age at which peak bone mass is attained the loss of bone mass in hormonally sufficient women and men can be directly associated with
oxidative stress.
An imbalance between the production of reactive oxygen species and the ability to neutralize them is referred to as _______________ ________________ This condition can lead to deleterious structural and functional changes to lipids, proteins and DNA if the reactive oxygen species are not neutralized (aka, scavenged). These structural and functional changes are referred to as _________________ ________________
oxidative stress; oxidative damage
What is meant by the term "gene mutation"?
permanent change in DNA sequence
The maximum isometric force of fully activated skeletal muscle following eccentric contraction is greater than the maximum isometric force produced with the muscle at the same muscle length prior to the stretch. What is the term that describes this?
residual force enhancement
List four of the most studied animal models:
roundworms, fruit flies, non-human primates, birds
Exercise by postmenopausal women can increase the bone mineral density at the lumbar spine and at the femoral neck. Although the increases in bone mineral density seem small they are biomechanically important. Why?
small increases in bone density can result in large increases in bone strength
Some mammalian somatic cells such as stem cells and cancer cells may circumvent the shortening of chromosomes during replication due to the activity of a specific enzyme. What is the name of the enzyme?
telomerase
What is the name of the structure that reaches a "critical length" at which time a cell reaches its Hayflick limit?
telomere
Why have the published studies reviewed in class and related to caloric restriction in non-human primates been unable to report that caloric restriction increases maximum lifespan?
the durations of experiments were not long enough
The overall length of cell nuclear chromosomes (excluding stem cells) become shorter after each cell division. The shortening occurs because the DNA replication process is unable to copy the ends of the linear chromosomes. What is the name of the inability of the process to copy the ends of the chromosomes?
the end replication problem
Name a valid biomarker of aging.
there are none
What best explains the age-related preservation of eccentric force generation compared to isometric and concentric force generation?
titin
What is the primary contributor to the stiffness of passively stretched sarcomeres?
titin
Based on the article by Mather et al. (2011), in order to be valid, a biomarker of aging must meet the following key criteria: ☐ work in humans, animal models and plant models ☐ be repeatedly measurable without inducing harm ☐ estimate the rate of chronological aging ☐ monitor a basic aging process ☐ secondarily monitor the effects of disease
☐ be repeatedly measurable without inducing harm ☐ monitor a basic aging process