LIFESPAN EXAM 2 – GEROSCIENCE AND MECHANISMS
OF AGING COMPLETE QUESTIONS WITH 100%
CORRECT ANSWERS
1 Which cellular process is most directly impaired by mutations in the
WRN gene, leading to features of premature aging in Werner
syndrome
A) Telomere lengthening via telomerase
B) Homologous recombination repair of DNA double-strand breaks
C) Resolution of G-quadruplex structures during DNA replication
D) Mitochondrial base excision repair
Correct Answer C
Detailed explanation WRN protein is a RecQ helicase essential for
resolving G-quadruplex and other complex DNA structures that stall
replication forks In Werner syndrome defective WRN causes replication
stress accelerated cellular senescence and progeroid features While
WRN participates in homologous recombination its failure to resolve G-
quadruplexes is the primary driver of genomic instability in this disorder
2 In a longitudinal study of centenarians which biomarker at age 70 is
the strongest independent predictor of reaching age 100
A) Low fasting glucose
B) High LDL cholesterol
C) High C-reactive protein
D) Low grip strength
,Correct Answer A
Detailed explanation Longitudinal data including the New England
Centenarian Study show that lower fasting glucose even within normal
range at age 70 strongly predicts exceptional longevity independent of
BMI or smoking Chronic low-grade inflammation high CRP and low
muscle strength are negative predictors while high LDL is not protective
3 Which dietary intervention has been most consistently shown to
extend maximal lifespan in rodents without genetic modification
A) Intermittent fasting with ad libitum feeding on alternate days
B) 40 percent caloric restriction from weaning
C) High-protein low-carbohydrate ketogenic diet
D) Methionine restriction starting in middle age
Correct Answer B
Detailed explanation Lifelong 40 percent caloric restriction remains the
gold standard for extending both median and maximal lifespan in
rodents reducing age-related diseases across multiple organ systems
Intermittent fasting and methionine restriction can extend lifespan but
less consistently than classical caloric restriction Ketogenic diets do not
consistently extend maximal lifespan
4 Which of the following is a hallmark feature of replicative
senescence in human fibroblasts
A) Loss of p16INK4a expression
B) Telomere shortening below a critical length
C) Increased telomerase activity
D) Escape from apoptosis despite DNA damage
Correct Answer B
Detailed explanation Human somatic fibroblasts lack sufficient
,telomerase Telomeres shorten with each division Once a subset of
telomeres reaches a critically short length the DNA damage response
activates p53 and p21 leading to irreversible replicative senescence
Upregulation of p16INK4a occurs not loss
5 In the context of inflammaging which cytokine shows the most
consistent elevation with age across human populations
A) Interleukin-2
B) Interleukin-6
C) Transforming growth factor beta
D) Interferon gamma
Correct Answer B
Detailed explanation Interleukin-6 rises steadily with age in serum and
tissues contributing to sarcopenia atherosclerosis and cognitive decline
It is a robust biomarker of inflammaging and a predictor of all-cause
mortality in older adults The other cytokines show variable or less
consistent age-related increases
6 A 75-year-old woman with sarcopenia begins resistance training
three times per week for six months Which cellular change is most
likely to occur in her muscle
A) Increase in myonuclear domain size without new nuclei
B) Satellite cell activation and myonuclear accretion
C) Conversion of type I fibers to type II fibers
D) Reduction in mitochondrial biogenesis
Correct Answer B
Detailed explanation Resistance training in older adults activates
satellite cells which fuse with existing myofibers to provide new
myonuclei This myonuclear accretion supports protein synthesis and
, hypertrophy Aging impairs but does not abolish this capacity
Myonuclear domain size is relatively stable
7 Which genetic variant is most strongly associated with human
exceptional longevity in multiple genome-wide association studies
A) APOE epsilon4 allele
B) FOXO3A single nucleotide polymorphism rs2802292
C) TERT promoter mutation
D) MTOR CAG repeat expansion
Correct Answer B
Detailed explanation FOXO3A variants consistently associate with
survival to age 90 and older across Japanese European and African
American cohorts The variant modulates stress resistance and insulin
signaling APOE epsilon4 is a risk factor for early mortality not longevity
8 Which statement best describes the role of autophagy in aging
A) Autophagy decreases uniformly in all tissues with age leading to
proteotoxicity
B) Basal autophagy is harmful in postmitotic neurons and should be
suppressed
C) Genetic enhancement of autophagy extends lifespan in multiple
species
D) Autophagy only clears protein aggregates not damaged organelles
Correct Answer C
Detailed explanation Upregulating autophagy through genetic means
for example Atg7 overexpression or beclin1 mutants extends lifespan in
worms flies and mice Autophagy declines with age but not uniformly
and its enhancement improves healthspan by clearing damaged
mitochondria and aggregated proteins
OF AGING COMPLETE QUESTIONS WITH 100%
CORRECT ANSWERS
1 Which cellular process is most directly impaired by mutations in the
WRN gene, leading to features of premature aging in Werner
syndrome
A) Telomere lengthening via telomerase
B) Homologous recombination repair of DNA double-strand breaks
C) Resolution of G-quadruplex structures during DNA replication
D) Mitochondrial base excision repair
Correct Answer C
Detailed explanation WRN protein is a RecQ helicase essential for
resolving G-quadruplex and other complex DNA structures that stall
replication forks In Werner syndrome defective WRN causes replication
stress accelerated cellular senescence and progeroid features While
WRN participates in homologous recombination its failure to resolve G-
quadruplexes is the primary driver of genomic instability in this disorder
2 In a longitudinal study of centenarians which biomarker at age 70 is
the strongest independent predictor of reaching age 100
A) Low fasting glucose
B) High LDL cholesterol
C) High C-reactive protein
D) Low grip strength
,Correct Answer A
Detailed explanation Longitudinal data including the New England
Centenarian Study show that lower fasting glucose even within normal
range at age 70 strongly predicts exceptional longevity independent of
BMI or smoking Chronic low-grade inflammation high CRP and low
muscle strength are negative predictors while high LDL is not protective
3 Which dietary intervention has been most consistently shown to
extend maximal lifespan in rodents without genetic modification
A) Intermittent fasting with ad libitum feeding on alternate days
B) 40 percent caloric restriction from weaning
C) High-protein low-carbohydrate ketogenic diet
D) Methionine restriction starting in middle age
Correct Answer B
Detailed explanation Lifelong 40 percent caloric restriction remains the
gold standard for extending both median and maximal lifespan in
rodents reducing age-related diseases across multiple organ systems
Intermittent fasting and methionine restriction can extend lifespan but
less consistently than classical caloric restriction Ketogenic diets do not
consistently extend maximal lifespan
4 Which of the following is a hallmark feature of replicative
senescence in human fibroblasts
A) Loss of p16INK4a expression
B) Telomere shortening below a critical length
C) Increased telomerase activity
D) Escape from apoptosis despite DNA damage
Correct Answer B
Detailed explanation Human somatic fibroblasts lack sufficient
,telomerase Telomeres shorten with each division Once a subset of
telomeres reaches a critically short length the DNA damage response
activates p53 and p21 leading to irreversible replicative senescence
Upregulation of p16INK4a occurs not loss
5 In the context of inflammaging which cytokine shows the most
consistent elevation with age across human populations
A) Interleukin-2
B) Interleukin-6
C) Transforming growth factor beta
D) Interferon gamma
Correct Answer B
Detailed explanation Interleukin-6 rises steadily with age in serum and
tissues contributing to sarcopenia atherosclerosis and cognitive decline
It is a robust biomarker of inflammaging and a predictor of all-cause
mortality in older adults The other cytokines show variable or less
consistent age-related increases
6 A 75-year-old woman with sarcopenia begins resistance training
three times per week for six months Which cellular change is most
likely to occur in her muscle
A) Increase in myonuclear domain size without new nuclei
B) Satellite cell activation and myonuclear accretion
C) Conversion of type I fibers to type II fibers
D) Reduction in mitochondrial biogenesis
Correct Answer B
Detailed explanation Resistance training in older adults activates
satellite cells which fuse with existing myofibers to provide new
myonuclei This myonuclear accretion supports protein synthesis and
, hypertrophy Aging impairs but does not abolish this capacity
Myonuclear domain size is relatively stable
7 Which genetic variant is most strongly associated with human
exceptional longevity in multiple genome-wide association studies
A) APOE epsilon4 allele
B) FOXO3A single nucleotide polymorphism rs2802292
C) TERT promoter mutation
D) MTOR CAG repeat expansion
Correct Answer B
Detailed explanation FOXO3A variants consistently associate with
survival to age 90 and older across Japanese European and African
American cohorts The variant modulates stress resistance and insulin
signaling APOE epsilon4 is a risk factor for early mortality not longevity
8 Which statement best describes the role of autophagy in aging
A) Autophagy decreases uniformly in all tissues with age leading to
proteotoxicity
B) Basal autophagy is harmful in postmitotic neurons and should be
suppressed
C) Genetic enhancement of autophagy extends lifespan in multiple
species
D) Autophagy only clears protein aggregates not damaged organelles
Correct Answer C
Detailed explanation Upregulating autophagy through genetic means
for example Atg7 overexpression or beclin1 mutants extends lifespan in
worms flies and mice Autophagy declines with age but not uniformly
and its enhancement improves healthspan by clearing damaged
mitochondria and aggregated proteins
