Biology of Human Aging - Lecture 13

Q: In Study 1, how far apart do identical (MZ) twins die?

A: 6 years / 10 months apart.

Q: In Study 1, how far apart do fraternal (DZ) twins die?

A: 8 years / 5 months apart.

Q: Where was Study 1 conducted?

A: On all twins in New York City over a period of time.

Q: In Study 2, how far apart did identical twins die?

A: 14.1 years.

Q: In Study 2, how far apart did non-identical twins die?

A: 18.5 years.

Q: In Study 2, how far apart did two random individuals die?

A: 19.2 years.

Q: According to Study 3 (largest study), how far apart do identical twins die on average?

A: ~36 months apart.

Q: According to Study 3, how far apart do fraternal twins die on average?

A: ~75 months apart.

Q: According to Study 3, how far apart do siblings die on average?

A: ~106 months apart.

Q: What did twin studies show about life expectancy (LE) and cause of death?

A: LE and cause of death are more likely to be closer or similar in MZ twins than DZ twins.

Q: Are these genetic influences unique to twins?

A: No, adoptive children’s studies also indicate that we can inherit different susceptibility to diseases.

Q: What proportion of disease predisposition in the general population is heritable?

A: About 30%.

Q: Between genetics and environment, which is the stronger influence on disease and longevity?

A: Environment is stronger (70%), but genetics does play a role (30%).

Q: What was the purpose of adoptive children’s studies in aging research?

A: To separate Nature vs Nurture (DNA vs Environment); the study showed cause of death was influenced by genetics.

Q: Why are twin studies considered the best for studying genetic influence?

A: Because if there are more similarities between MZ than DZ twins, it suggests a strong influence by genetic factors, since MZ share 100% of their genes and DZ/siblings share less.

Q: How did age at death compare between MZ twins, DZ twins, and the general population?

A: Age at death seemed related to genetics, with MZ twins dying closer in age than DZ twins or the general population.

Q: What question remains about cause of death in twins?

A: Do we find a correlation between cause of death and genetics?

Q: Between genetics and environment, which has a stronger influence on longevity and disease, even in identical twins?

A: Environment is stronger (70%), but genetics does play a role (30%).

Q: Do MZ twins necessarily have the same diseases or age the same way?

A: No, MZ twins do not necessarily have the same diseases and they age differently.

Q: For heritable cancers (breast, colorectal, prostate), what is the absolute risk of the same disease occurring before age 75 in an MZ twin whose co-twin had it?

A: Only 9–21%.

Q: Which disease appears to have a stronger genetic component?

A: Cardiovascular (CV) disease.

Q: In a long-term study, what was the risk of a man dying of CV disease like his co-twin?

A: Less than 50%.

Q: What does this suggest about very heritable diseases?

A: Even in very heritable diseases, important non-genetic factors influence disease outcomes in DNA-identical twins.

Q: What are examples of environmental factors that influence disease and aging?

A: External factors in early development and early adulthood.

Q: Why would a genetic pattern in one identical twin likely be present in the other?

A: Because identical twins are genetically virtually identical.

Q: How can we tell if a characteristic is related to genetics in twins?

A: If a characteristic identified in one twin is caused by certain genes, it would very likely also be present in the other twin; the concordance rate helps suggest this.

Q: What is concordance in twin studies?

A: Concordance is when both twins share a trait or disease; it helps indicate whether a trait or disease is related to genetics.

Q: How can comparing concordance rates between identical and fraternal twins help?

A: It can help suggest whether a disease or certain trait has a genetic cause.

Q: How can comparisons of dizygotic and monozygotic twins be used in research?

A: To assess the importance of genetic and environmental factors in producing differences in a characteristic.

Q: How is concordance for a trait assessed in twins?

A: By calculating the concordance rate for the trait.

Q: What does it mean if both members of a twin pair have a trait?

A: The twins are concordant for that trait.

Q: What does it mean if only one member of a twin pair has a trait?

A: The twins are discordant for that trait.

Q: What is concordance?

A: Concordance is the percentage of twin pairs that are concordant for a trait.

Q: How is concordance rate calculated?

A: Concordance Rate = # of concordant pairs / total # of pairs.

Q: What does it indicate if MZ concordance is significantly higher than DZ concordance?

A: The disorder has a genetic component.

Q: What does it indicate if MZ concordance is the same or similar to DZ concordance?

A: The disorder is environmentally caused.

Q: What does it indicate if MZ concordance is 100%?

A: The disorder is genetically caused.

Q: What does it indicate if MZ concordance is significantly less than 100%?

A: The disorder has an environmental component.

Q: What does a concordance closer to 100% for MZ twins indicate?

A: Strong genetic influence.

Q: What does a concordance closer to 0% for MZ twins indicate?

A: Strong environmental influence.

Q: If MZ concordance is higher than DZ concordance, what does it suggest?

A: The trait or disorder has a greater genetic component.

Q: Name some mental or physical diseases that have a high genetic component based on concordance studies.

A: Autism, Alzheimer’s Disease, Rheumatoid Arthritis.

Q: What does it indicate if MZ and DZ concordance are both closer to 0% for a disease like breast cancer?

A: Low genetic component and higher environmental factor.

Q: Which mental disease shows higher concordance in males than females, indicating a genetic influence?

A: Alcoholism.

Q: What does autism concordance suggest about its cause?

A: Autism shows a genetic component.

Q: What does breast cancer concordance suggest about its cause?

A: Breast cancer shows an environmental factor.

Q: How can the genetic influence on a trait like arthritis be estimated?

A: By comparing studies of monozygotic (MZ) and dizygotic (DZ) pairs of twins.

Q: What does it indicate if twins in a monozygotic pair are much likelier to match in arthritis than dizygotic twins?

A: The trait has a strong genetic component.

Q: What does a concordance closer to 100% for MZ twins indicate?

A: Stronger genetic influence.

Q: What does a concordance closer to 0% for MZ twins indicate?

A: Stronger environmental influence.

Q: If MZ concordance is higher than DZ concordance, what does it suggest?

A: The trait has a greater genetic component.

Q: What is the incidence of schizophrenia in the general population?

A: 1%.

Q: What is the incidence of schizophrenia in siblings of someone diagnosed?

A: 9%.

Q: What is the incidence of schizophrenia in dizygotic (DZ) twins of someone diagnosed?

A: 17%.

Q: What is the incidence of schizophrenia in monozygotic (MZ) twins of someone diagnosed?

A: 48%.

Q: What does this data suggest about the inheritance of schizophrenia?

A: Inheritance plays a part, but doesn’t determine everything; otherwise, identical twins would be at 100%.

Q: What are progerias?

A: “Premature aging diseases”; genetic disorders that hint at genetic control over aging (“pro” = before, “geras” = old age).

Q: How many main diseases mimic natural aging?

A: Three.

Q: Name the three main progeria diseases that mimic natural aging.

A: Hutchinson-Gilford (HGS), Werner Syndrome (WS), Down Syndrome (DS).

Q: How rare is Hutchinson-Gilford Syndrome (HGS)?

A: Extremely rare, 1 in 8 million births.

Q: When does HGS appear?

A: Hits in infancy; born normal, develop by age 7, but changes can be detected by age 1.

Q: How many individuals with HGS exist worldwide?

A: Less than 100.

Q: How much faster is the aging process in HGS?

A: Accelerated 8–10×.

Q: What are some growth and physical characteristics of HGS?

A: Growth retardation, short stature, thin, characteristic facial appearance (large cranium, small jaw).

Q: Which races and genders are affected by HGS?

A: Affects all races and both genders, slightly more males than females; 97% Caucasian.

Q: Name age-related characteristics of HGS.

A: Loss of hair (baldness), thin/dry/wrinkled skin (loss of subcutaneous fat), muscle wasting, age spots, infertility, stiffness of joints, kidney failure.

Q: What cardiovascular and cerebrovascular diseases are common in HGS?

A: Heart attacks, strokes, hypertension, angina, and congestive heart failure, especially at end stages.

Q: What are typical cholesterol levels in individuals with HGS?

A: Normal LDL levels but decreased HDL.

Q: How does the cardiovascular system of HGS patients resemble arteriosclerosis?

A: Calcium deposits cause vascular stiffening, hypertension, and plaque formation, even with normal cholesterol levels.

Q: What is the median age of death for HGS patients?

A: Around 11–14 years.

Q: How aged are the arteries of a 9-year-old with HGS?

A: Similar to those of a 70-year-old.

Q: What are the usual causes of death in HGS?

A: Congestive heart failure, heart attacks, or strokes, typically around age 13 but as early as 4.

Q: What condition develops in HGS that mimics some age-related changes?

A: Arthritis.

Q: Why is HGS called a “segmental” aging disorder?

A: Because it mimics some aspects of aging but misses others; some parts of development are missed, while others are sped up.

Q: What do we know about the cause of HGS?

A: It appears to be genetic in nature, caused by a pinpoint mutation in a single gene.

Q: Does HGS run in families?

A: No, parents and siblings of affected individuals typically do not show the disease.

Q: How does the mutation in HGS arise?

A: Random spontaneous mutation in sperm.

Q: What is the inheritance pattern of HGS?

A: Autosomal dominant.

Q: Do males with Hutchinson-Gilford Syndrome (HGS) develop prostate problems like in normal aging?

A: No.

Q: Do individuals with HGS have an increased risk of cancer or cataracts?

A: No.

Q: How common is diabetes in HGS?

A: Rare.

Q: Do individuals with HGS get Alzheimer’s disease or suffer mental degeneration?

A: No.

Q: What does this tell us about HGS as a model for aging?

A: HGS mimics some age-related changes but differs in key aspects, so it is a partial (segmental) model for aging.

Q: What type of disorder is Hutchinson-Gilford Syndrome (HGS) now classified as?

A: A new kind of laminopathy.

Q: When was a clinical and molecular update on HGS published?

A: June 2002.

Q: What were the ages of the youngest patients mentioned in the update?

A: 6 and 4 years old.

Q: Who was the oldest known progeria patient at the time?

A: Susana Lopez, 21 years old.

Q: When does Werner Syndrome typically develop?

A: It develops in late adolescence, around age 15–20; more of an adult progeria.

Q: What happens after puberty in individuals with Werner Syndrome?

A: They rapidly start to age.

Q: How rare is Werner Syndrome?

A: Occurs in about 3 in 1 million individuals.

Q: What is the typical lifespan of someone with Werner Syndrome?

A: 47–50 years.

Q: What is the inheritance pattern of Werner Syndrome?

A: Rare autosomal recessive disease.

Q: Name some early age-related characteristics of Werner Syndrome.

A: Grey/white hair, wrinkled skin, age spots, early infertility (~30), short stature, thinning skin, muscle wasting/loss of muscle mass.

Q: In which country did about ¾ of Werner Syndrome cases occur?

A: Japan.

Q: Why was Werner Syndrome more common in Japan historically?

A: Marriages between first cousins were common.

Q: Can Werner Syndrome affect more than one child in a family?

A: Yes, it can affect multiple children and is heritable.

Q: What eye condition do WS patients develop, and when?

A: Cataracts in both eyes around age 30.

Q: Name some age-related conditions that develop in WS.

A: Atherosclerosis, severe osteoporosis (lower limbs), type II diabetes, relatively high number of cancers (mostly rare soft tissue types), thinning of bone, diminished fertility.

Q: What age-related diseases do WS patients not develop?

A: Alzheimer’s disease and prostate problems.

Q: What are the most common causes of death in WS?

A: Cancer and cardiovascular (C.V.) disease.