Topics
• Functional Assessment of the Elderly
• Biomarkers of Aging
• Cellular Senescence– Lecture PowerPoint to be posted on website
Geriatric AssessmentInvolves a multi-dimensional diagnostic process designed
to qualify an elderly individual in terms of:
• Functional capabilities• Disabilities
• Medical & Psychological characteristics
A list of typical assessments is summarized in Table 3.3
For our discussion, we will consider particularly: • Activities of Daily Living (ADL)
• Instrumental Activities of Daily Living (IADL) **See Table 3.4**
Functional Assessment
1. Tests examining general physical health
2. Tests measuring ability to perform basic self care (ADLs)
3. Tests measuring ability to perform more complex activities (IADLs), reflecting the ability to live independently in the community
The severity of the disability may be measured in terms
of whether a person:
• Does not perform the activity at all
• Can only perform the activity with the help of another
person
• Can perform the activity with the help of special equipment
Table 3-4 Categories of Physical Health Index MeasuringPhysical Competence
ACTIVTIES INSTRUMENTAL ACTIVITIESOF DAILY LIVING OF DAILY LIVING
Feeding CookingBathing CleaningTo ileting Using telephoneDressing WritingAmbulation ReadingTr ansfer from toilet LaundryVisual acuity Driving a carOthers Others
Figure 3. 6: % of persons 70 years & older having difficulty/inability to perform ADLs & IADLs
With advancing age, 1) disability intensity increases in men & women; 2) disability intensity is higher in women than in men at the same age (esp. at later ages); 3) females live a longer average life span but live longer with disability
Table 3-6 Physiologic Parameters in Aging, Physical Inactivity Weightlessness (In Space) Reduced Increased
Maximum oxygen consumption Systolic blood pressure and peripheral resistance
Resting and maximum cardiac output Vestibular sensitivity Stroke volume Serum total cholesterol Sense of balance Urinary nitrogen and creatinine Body water and sodium Bone calcium Blood cell mass Lean body mass Glucose tolerance test Variable Sympathetic activity and neurotransmission Endocrine changes Thermoregulation Altered EEG Immune responses Altered sleep
Changes in specific senses
Questions
1. What are the components of Geriatric Assessment?
2. What are the categories of these assessment programs
3. What are the differences between ADL’s and IADL’s? Provide some examples
4. Discuss the idea that women have more disability than men
5. Explain compression of morbidity
How genetic susceptibility may influence a disease:
• By itself
• By making the carrier more susceptible to disease
• By increasing the expression of a risk factor, or the risk factor may increase the genetic effects
Disease as a tool for the study of aging
• Sporadic cases of syndromes having multiple characteristics of premature (early onset, 20-30 years of age) or accelerated (rapid progression) aging occur in humans
These conditions are grouped under the name of progeria.
Examples of progeria syndromes are Werner’s syndrome (WS) and Hutchinson-Guildford
syndrome
Differences between WS & Aging
WS
• Rare
• NO hypertension
• NO dementia
• Tissue calcifications
Aging
•Universal
•Hypertension
•Dementia
•NO tissue calcifications
Questions
1. What are three ways that genetic susceptibility influences disease?
2. What is progeria?3. What is a biomarker and how can progeria
be used as one?4. What are some characteristics of WS?5. List the differences between diseases and
aging
Senescence
• Replicative Senescence
• Cellular Senescence
• Senescent Phenotype
• Cellular Senescence and Cancer
• Senescence and Aging
• Antagonistic Pleiotropy
First description: the Hayflick limit
Pro
lifer
ativ
e ca
paci
ty
Number of cell divisions
FiniteReplicativeLife Span"Mortal"
InfiniteReplicativeLife Span"Immortal"
EXCEPTIONSGerm line
Early embryonic cells (stem cells)Many tumor cells
What happens when cells exhaust their replicative life span
What happens when cells exhaust their replicative life span
REPLICATIVE SENESCENCE
•Irreversible arrest of cell proliferation(universal)
•Resistance to apoptosis(stem cells)
•Altered function(universal but cell type specific)
SENESCENT PHENOTYPE
Cellular Senescence
What causes it?(what causes the senescent phenotype?)
Cell proliferation (replicative senescence)= TELOMERE SHORTENING
DNA damage
Oncogene expression
Supermitogenic signals
What do inducers of the senescentphenotype have in common?
Inducers of cellular senescence
Cell proliferation(short telomeres)
DNA damage
Oncogenes
Strong mitogens
PotentiallyCancerCausing
Normal cells(mortal)
Immortal cells(precancerous)Inducers
of senescence
Cell senescence Transformation Apoptosis
Tumor suppressor mechanisms
Cellular SenescenceAn important tumor suppressor mechanism
•Induced by potentially oncogenic events
•Most tumor cells are immortal
•Many oncogenes act by allowing cells to bypassthe senescence response
•Senescence is controlled by the two most importanttumor suppressor genes -- p53 and pRB
•Mice with cells that do not senesce die youngof cancer
Cellular SenescenceAn important tumor suppressor mechanism
What does cellular senescence have to do with aging?
•The senescent phenotype entails changes in cell function
•Aging is a consequence of the declining forceof natural selection with age
Aging before cell phones ……
100%
Su
rviv
ors
AGE
Natural environment: predators, infections, external hazards, etcMost of
humanevolution
Modern, protectedenvironment
(very VERY recent)
Antagonistic pleiotropy:Some traits selected to optimize fitness in young
organisms can have unselected deleteriouseffects in old organisms
(what's good for you when you're young may be bad for you when you're old)