1 / 23

MCB 135K Discussion

MCB 135K Discussion. February 2, 2005. Topics. Functional Assessment of the Elderly Biomarkers of Aging Cellular Senescence Lecture PowerPoint to be posted on website. Geriatric Assessment.

ahanu
Download Presentation

MCB 135K Discussion

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. MCB 135K Discussion February 2, 2005

  2. Topics • Functional Assessment of the Elderly • Biomarkers of Aging • Cellular Senescence • Lecture PowerPoint to be posted on website

  3. Geriatric Assessment Involves 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**

  4. Tests examining general physical health Tests measuring ability to perform basic self care (ADLs) 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 Functional Assessment

  5. 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

  6. A theory of “compression” of morbidity (rectangularization of survivorship) curve

  7. Questions • What are the components of Geriatric Assessment? • What are the categories of these assessment programs • What are the differences between ADL’s and IADL’s? Provide some examples • Discuss the idea that women have more disability than men • Explain compression of morbidity

  8. 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

  9. 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

  10. Differences between WS & Aging WS • Rare • NO hypertension • NO dementia • Tissue calcifications • Aging • Universal • Hypertension • Dementia • NO tissue calcifications

  11. Questions • What are three ways that genetic susceptibility influences disease? • What is progeria? • What is a biomarker and how can progeria be used as one? • What are some characteristics of WS? • List the differences between diseases and aging

  12. Senescence • Replicative Senescence • Cellular Senescence • Senescent Phenotype • Cellular Senescence and Cancer • Senescence and Aging • Antagonistic Pleiotropy

  13. Cellular Senescence What is it? Response of normal cells to potentially cancer-causing events

  14. First description: the Hayflick limit Finite Replicative Life Span "Mortal" Infinite Replicative Life Span "Immortal" Proliferative capacity Number of cell divisions EXCEPTIONS Germ line Early embryonic cells (stem cells) Many tumor cells What happens when cells exhaust their replicative life span

  15. 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

  16. 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 senescent phenotype have in common?

  17. Inducers of cellular senescence Cell proliferation (short telomeres) Potentially Cancer Causing DNA damage Oncogenes Strong mitogens Normal cells (mortal) Immortal cells (precancerous) Inducers of senescence Cell senescence Transformation Apoptosis Tumor suppressor mechanisms

  18. Cellular Senescence An important tumor suppressor mechanism • Induced by potentially oncogenic events • Most tumor cells are immortal • Many oncogenes act by allowing cells to bypass • the senescence response • Senescence is controlled by the two most important • tumor suppressor genes -- p53 and pRB • Mice with cells that do not senesce die young • of cancer

  19. Cellular Senescence An 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 force • of natural selection with age

  20. Aging before cell phones …… Modern, protected environment (very VERY recent) 100% Natural environment: predators, infections, external hazards, etc Survivors Most of human evolution AGE Antagonistic pleiotropy: Some traits selected to optimize fitness in young organisms can have unselected deleterious effects in old organisms (what's good for you when you're young may be bad for you when you're old)

  21. Questions • What causes cellular senescence, what are the inducers and what do they have in common? • What is replicative senescence? • List 3 characteristics of the senescent phenotype • What is the relationship between carcinogenesis, aging, and senescence? • Explain antagonistic pleiotropy

More Related