SCIE 634
Biology of Aging

Jason Wolfe

Course Description

"People in the U.S. are living longer than ever before. Many seniors live active and healthy lives. But there's no getting around one thing: as we age, our bodies and minds change" (from Medline, Seniors' Health). This course will consider 4 important questions: What are the changes to body and mind that take place during aging? What are the causes of the major diseases that afflict the elderly and what research avenues point to prospects for treatment? What research is being done to explore the underlying basis of the aging process? What are the prospects for intervention in the aging process, thereby extending lifespan?

Each class meeting will be divided into two parts. One part will be a lecture providing a conceptual introduction to a specific topic (shown below in bold). The second part will involve a student-led class discussion of a recent review article on the subject introduced by a lecture. One day (or more) is scheduled between the introduction, and the student presentation on that topic. This is to give students time to make use of the information introduced in lecture to provide increased comprehension while reading the review article, and it also allows us to build on a subject over a two day period of time.

Lectures and Discussions
Introduction to Aging and the Elderly; Our aging society: measuring lifespan; centenarians; how to study aging; senescence. Cellular senescence; regulated cell death (apoptosis and autophagy)
Diabetes Cell Senescence and Cell Death
Vicencio et al (2008)
McBride (2008)
Alzheimer's Disease Diabetes
Marquess (2008)
Miller & Adeli (2008)
Osteoporosis Alzheimer's Disease
Small & Duff (2008)
Sano et al (2008)
Heart Disease Osteoporosis
Gallagher (2008)
Cancer Heart Disease
Shibata & Glass (2008)
Nicholls (2008)
Caloric restriction and model systems Cancer
DePinho RA (2000)
Hsu & Sabatini (2008)
Genetic diseases of premature aging Caloric restriction
Kennedy et al (2008)
Guarente (2008)
Free radicals, oxidative damage and aging Progeria
Martin et al (2008
Wang & Sun (2008)
Stem cell biology and aging Free radicals
Willcox et al (2008)
Lesnefsky & Hoppel (2008)
An evolutionary perspective on aging Stem cells
Yunis et al (2006)
Warren & Rossi (2008)
Lecture Topics

Our aging society; changing life spans; centenarians; how to study aging
What is an aging society?
What can we learn about aging from the oldest old?
What approaches are used to study aging?

Aging and senescence
What is the difference between getting old and aging?
What are the differences in the patterns of aging among different species?
Cellular senescence, regulated cell death (apoptosis and autophagy) and aging
How do cells age, or die of old age?
Does cellular aging or cellular death contribute to organismic aging?

What is the cause of the diabetes epidemic?
How does diabetes affect the aging process?

Alzheimer's Disease
What is the evidence that supports the amyloid hypothesis of AD?
What are the prospects for medical intervention in AD?

Heart Disease
How do atherosclerotic plaques form
What role does HDL play in retarding heart disease

What is the somatic mutation theory of cancer formation?
Do somatic mutations contribute to aging?
Bones, joints, arthritis and osteoporosis
How do arthritis and osteoporosis affect the elderly?
What causes arthritis and osteoporosis?

Caloric restriction and model systems
How does modulating caloric intake affect longevity?
What can be learned from genetic studies on yeast, nematodes and flies?

Genetic diseases of premature aging
What do progeric human diseases teach us about aging?
What do we learn from mutations that accelerate aging in mice?

The free radical theory of aging
How does cellular metabolism affect aging?
Do mitochondria play a role in aging?

Stem cell biology and its therapeutic potential
What recent developments in stem cell research reduce the ethical concerns associated with embryonic stem cells?
How might stem cell research address problems in aging?

How can aging be reconciled with Darwinism?
How does evolutionary theory of aging fit with research findings on the basis of aging?

Ending aging - visions of the future
Can aging be prevented?
What would extended life spans mean medically, socially, politically and economically?

Resources for Class Discussion

Bronwen M, Golden E, Carlson OD, Egan JM, Mattson MP, & Mauldsley S, (2008) Ageing Research Reviews 7:209–224.Caloric restriction: Impact upon pituitary function and reproduction.

Campisi J, (2008) Aging Cell 7:281-284
Aging and Cancer Cell Biology, 2008.

DePinho RA, (2000) Nature 408:248-254
The age of cancer.

Fröjdö S, Vidal H &Pirol L, (2008) BBA in press
Alterations of insulin signaling in type 2 diabetes: A review of the current evidence from humans.

Gallagher JC, (2008) Maturitas 60:65-69
Advances in bone biology and new treatments for bone loss

Gazit R, Weissman IL & Rossi DJ, (2008) Seminars in Hematology 45:218 - 224 R
Hematopoietic Stem Cells and the Aging Hematopoietic System

Guarente L, (2007) Cold Spring Harbor SQB 72:483-8.
Sirtuins in aging and disease.

Hsu PP & Sabatini DM (2008) Cell 134:703-7 
Cancer cell metabolism: Warburg and beyond.

Jackson RD & Shidham S, (2007) Curr Osteoporos Rep. 5:153-9
The role of hormone therapy and calcium plus vitamin D for reduction of bone loss and risk for fractures: lessons learned from the Women's Health Initiative.

Kennedy BK, Steffen KK & Kaeberlein M, (2007) Cell. Mol. Life Sci. 64:1323–1328.
Ruminations on dietary restriction and aging.

Lesnefsky EJ & Hoppel CL (2006) Ageing Research Reviews 5:402–433.
Oxidative phosphorylation and aging

Marquess JG, (2008) Consult Pharm. Suppl B:5-11
The elderly and diabetes: an age trend and an epidemic converging.

McBride H, (2008) J Cell Biol 183:757-759
Parkin mitochondria in the autophagosome.

Miller A & Adeli K, (2008) Current Opinion in Gastroenterology 24:204-209
Dietary fructose and the metabolic syndrome.

Nicholls SJ, (2008) Curr Opin Investig Drugs. 9:950-6
HDL: still a target for new therapies?

Sano M, Grossman H & Van Dyk K, (2008) CNS Drugs 22:887-902
Preventing Alzheimer's disease : separating fact from fiction.

Shibata N & Glass CK, (2008) J. Lipid Res. in press
Regulation of macrophage function in inflammation and atherosclerosis

Small SA & Duff K, (2008) Neuron 60:534-42
Linking Abeta and tau in late-onset Alzheimer's disease: a dual pathway hypothesis.

Vicencio JM et al, (2008) Gerontology 54:92-99
Senescence, Apoptosis or Autophagy? When a Damaged Cell Must Decide Its Path - A Mini-Review.

Wang Y & Sun L (2008) Ageing Research Reviews in press.
Current understanding of klotho

Bradley J. Willcox BJ , Curb JD & Rodriguez BL (2008) The American Journal of Cardiology, 10:Supplement 1, S75-S86
Antioxidants in cardiovascular health and disease: Key lessons from epidemiologic studies

Yunis EY, Zúñiga J, Koka PS, Husain Z, Romero V, Stern JNH, and Masha Fridkis-Harel MF, (2006) J Stem Cells 1:125–147.
Stem Cells in Aging: Influence of Ontogenic, Genetic and Environmental Factors