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GERO 499: Nutrition, genes, longevity and diseases

Spring/Summer 2011

Time: 2:00pm - 4:50pm Room: GER 230 for initial class, then Genoa Italy

Course Instructors:

Valter D. Longo, Ph.D.

Phone: (213)740-6212 Fax: (213)740-5714 E-mail: vlongo@usc.edu
Office Hours: By appointment in GERO 319

Please note that E-mail is the best way to be sure to contact the instructor

Course Description

This course is intended to teach students about the important role of nutrition and genes and the
impact each has on longevity and diseases, particularly diseases related to aging. This course is
unique in that it approaches these subjects through a traditional didactic approach as well as a
kinaesthetic approach to learning. This is accomplished by allowing students to have the opportunity
to learn in an environment that has proven to be conducive to healthy aging. What students learn in
the classroom about longevity they will see manifest in the local population of Genoa, Italy. This is
one of populations with the highest portion of people over 65 in the world. Students will be
encouraged to observe and compare the lifestyle choices people make through their activities of daily
living and dietary choices. Students will also be strongly encouraged to live as much as possible the
Mediterranean life style with emphasis on the Mediterranean diet and an active lifestyle. In particular
the class will try to emphasize the Mediterranean life style of 50-100 years ago, which is still adopted
by the older population but often not by younger individuals. For many students, this month-long
immersion in the Mediterranean life style, could have a life long impact.

In the classroom students will examine the effect of nutrition and genes modulated by nutrients on
aging and life span in simple organisms and humans. The course will provide an introduction to the
biology of aging and to the mechanisms for the extension of the healthy life span and the prevention
of age-related diseases. The course will also describe the effect of common but also extreme diets and
of diets adopted by very long-lived populations from around the world on aging and diseases.
Specific populations with unusually long life spans will be examined as part of the course. Finally the
course will discuss the role of diets, dietary restriction and fasting in the treatment of diseases with
emphasis on cancer, diabetes, cardiovascular and neurodegenerative diseases. Students will be given
actual case reports from doctors and/or clinical trials describing the translation of these approaches to
disease prevention and treatment. For example, they will learn about the effects of fasting on the side
effects caused by chemotherapy and they will see the effects of dietary restriction on hypertension
and diabetes. Students will be responsible for more in-depth study of selected topics through assigned
readings.

After class and on organized field trips, students will observe how typical Genoans live. Students will
make observations about how much exercise (e.g., walking, bicycling) they see people participating
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in, the types of transportation systems that influence these decisions, the kind of housing people live
in and the food that is typically purchased in markets and in restaurants.

To defray the expenses of the trip, students will be encouraged to apply for research fellowships to
perform spring/summer research related to the topics of the course.

Prerequisite
It is mandatory for students to have had at least 2 prior undergraduate-level courses in biology.

Course Objectives
By the conclusion of the course, students are expected to be able to:

1) Understand the fundamental biology underlying aging and age-related diseases.

2) Understand the role of different dietary components on gene expression, cell function and
protection, aging and diseases.
3) Describe the type of diets that can extend the healthy life span and why.
4) Understand how biogerontology can be applied to disease treatment and its role in medicine.
5) Have a general understanding of the role of different types of exercise on physiology, aging
and diseases.
6) Understand how to apply evolutionary and comparative biology approaches to the
optimization of health, disease prevention and treatment.
7) Understand the differences in the diet and lifestyle of people from Genoa Italy and
Americans. Students should be able to identify the differences that are known to affect aging
and diseases.

Students with Disabilities (the information below was provided by the office of the Provost)
“Any student requesting academic accommodations based on a disability is required to register with
Disability Services and Programs (DSP) each semester. A letter of verification for approved
accommodations can be obtained from DSP. Please be sure that the letter is delivered to any of the
Instructors as early in the semester as possible. DSP is located in on campus in STU 301, and is open
from 8:30 a.m. - 5:00 p.m., Monday through Friday. The phone number for DSP is (213) 740-0776.”

Statement on Academic Integrity

USC seeks to maintain an optimal learning environment. General principles of academic honesty
include the concept of respect for the intellectual property of others, the expectation that individual
work will be submitted unless otherwise allowed by an instructor, and the obligations both to protect
one’s own academic work from misuse by others as well as to avoid using another’s work as one’s
own. All students are expected to understand and abide by these principles. Scampus, the Student
Guidebook, contains the Student Conduct Code in Section 11.00, while the recommended sanctions
are located in Appendix A: http://www.usc.edu/dept/publications/SCAMPUS/gov/. Students will be
referred to the Office of Student Judicial Affairs and Community Standards for further review, should
there be any suspicion of academic dishonesty. The Review process can be found at:
http://www.usc.edu/student-affairs/SJACS/.

Textbook
None. Articles will be used instead of the textbook and distributed at the beginning of the class.

Student Evaluation
Students will be evaluated on the basis of:
1) Midterm (45%)
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2) Final (45%)
3) Attendance and participation (10%)
 Gero 499 CLASS SCHEDULE

Class will meet for at least three hours per day Monday through Thursday. At least two
Fridays during the four weeks will consist of mandatory field trips. One Friday is an
optional field trips organized for students.

WEEK 1 class meets on the USC Campus

Monday, May 30: Memorial Day Holiday

Tuesday, May 31: Meet in Room GER 124. Orientation to Class. Overview of Genoa,
Italy. Introduction to the class, format, travel and accommodations.

Reading: In Northern Italy, the Agony of Aging not so Gracefully. New York
Times Sept. 22 2006.
http://www.nytimes.com/2006/09/22/world/europe/22genoa.html

Wednesday, June 1: What is aging?: From the history of the quest for the fountain of
youth to aging theories.

Readings: Extending the Healthy Life span: from yeast to humans. Fontana, L,
Partridge, L., Longo VD. Science, April 16, 328, 321-6.

Thursday, June 2: Aging at the molecular, organelle, and cellular level.

Readings: Longo, VD, Finch CE. Evolutionary Medicine: from Starvation and
Dwarf Model Systems to Healthy Centenarians? Science 299, 2003, pp. 1342-
1346., Longo VD., Lieber, M., and Vijg, J. Turning Anti-aging genes against
Cancer. Nature Reviews Molecular Cell Biology, Nov. 2008, 902.

Friday , June 3d: Nutrients, genes and life span extension in worms and flies

Readings: Nutrients, genes and life span extension in worms and flies
Genes, the extension of the healthy lifespan and diseases in mammals (mice to
humans). : Extending the Healthy Life span: from yeast to humans. Fontana, L,
Partridge, L., Longo VD. Science, April 16, 2010, 328, 321-6. Longo, VD, Finch
CE. Evolutionary Medicine: from Starvation and Dwarf Model Systems to
Healthy Centenarians? Science 299, 2003, pp. 1342-1346

TRAVEL DAY: Monday-Tuesday, June 6-7

Week 2 Class meets at the University of Genoa Campus

Wednesday, June 8: Walking Tour of the City of Genoa/Orientation to City

Thursday, June 9: Nutrients, genes, and lifespan extension: from prokaryotes and yeast
to mammals.

Readings: Replicative aging in yeast: the means to the end. Steinkraus KA, Kaeberlein M,
Kennedy BK Annu Rev Cell Dev Biol. 2008;24:29-54. Review, Fabrizio P, Longo VD.
The chronological life span of Saccharomyces cerevisiae. Methods Mol Biol.
2007;371:89-95. e. Yan L et al 2007 Type 5 adenylyl cyclase disruption increases
longevity and protects against stress. Cell. 130:247-58. Extending the Healthy Life span:
from yeast to humans. Fontana, L, Partridge, L., Longo VD. Science, April 16, 2010, 328,
321-6

Friday, June 10: Optional Field Trip To Cinque Terre

Week 3: Class Meets on the University of Genoa Campus

Monday, June 13: Dietary restriction. This lecture will include a comparison of the
calorie intake in Italy and the US.

Readings: : Extending the Healthy Life span: from yeast to humans. Fontana, L,
Partridge, L., Longo VD. Science, April 16, 328, 321-6 Longo VD, Fontana L.
Calorie restriction and cancer prevention: metabolic and molecular mechanisms.
Trends Pharmacol Sci. 2010 Feb;31(2):89-98

Tuesday, June 14: Diet, aging and diseases: from the history of diets in Europe to the
diets of long-lived and short-lived populations from around the world. As part of this
lecture Dr. Longo and Italian guest speaker will talk about how nutrition changed in Italy
in the last 2000 years.

Readings: Finch CE. 2010 Jan 26;107 Suppl 1:1718-24. Epub 2009 Dec 4.
Evolution of the human lifespan and diseases of aging: roles of infection,
inflammation, and nutrition. Longo, VD, Finch CE. Evolutionary Medicine: from
Starvation and Dwarf Model Systems to Healthy Centenarians? Science 299,
2003, pp. 1342-1346. Longo VD, Fontana L. Calorie restriction and cancer
prevention: metabolic and molecular mechanisms. Trends Pharmacol Sci. 2010
Feb;31(2):89-98

Wednesday, June 15: Midterm Exam

Exercise. This lecture will include a comparison of the exercise and walking habits in
Italy and the US.
Readings: Exercise, aging and diseases Exercise and longevity. Studies in rats. Holloszy
JO. J Gerontol. 1988 Nov;43(6):B149-51. Review. Biological Mechanisms of Physical
Activity in Preventing Cognitive Decline. Lista et al Cell Mol Neurobiol (2010) 30:493–
503. Aging, training, and the brain: A review and future directions
Neuropsychol Rev. 2009 December ; 19(4): 504–522. Habitual exercise and vascular
ageing. Seals et al. J Physiol 587.23 (2009) pp 5541–5549

Thursday, June 16: Neurodegenerative diseases: from the fundamentals of the nervous
system, to the pathologies, to standard treatment to anti-aging and regenerative medicine
approaches for prevention and treatment. Students will relate this lecture to the visit in
San Martino Hospital where they will review either MRI or CT scans from patients with
neurodegenerative diseases. Dr. Tabaton, an internationally recognized expert in
Alzheimer disease will talk about his AD patients in Genoa and how the city cope with
this devastating disease.

Readings: Patient Case reports obtained from U of Genoa and USC clinicians will
be assigned to students and discussed in class.

a. Alzheimer’s disease: clinical trials and drug development. Mangialashe.

Lancet Vol 9 July 2010
b. Systematic Review: Factors Associated With Risk for and Possible Prevention
of Cognitive Decline in Later Life. Plassman, et al. Ann Intern Med.
2010;153:182-193
c. Probing the Biology of Alzheimer’s Disease in Mice. Ashe et al. Neuron 66,
June 10, 2010
d.
Surmeier DJ 2007 Calcium, ageing, and neuronal vulnerability in Parkinson's
disease.Lancet Neurol. 6:933-8. Review.

e. Thomas B, Beal MF. 2007 Parkinson's disease. Hum Mol Genet. Spec No.
2:R183-94.

Friday, June 17 Field Trip to San Martino Hospital

Week 4 Class Meets on the University of Genoa Campus

Monday, June 20: Cancer: from the mechanisms of tumorigenesis, to the pathologies, to
standard treatment to anti-aging approaches for its prevention and treatment.

Readings: Patient Case reports obtained from Gaslini Hospital in Genoa or USC
clinicians will be assigned to students and discussed in class.

a. Hanahan and Weinberg. The Hallmarks of Cancer. Cell, Vol. 100, 57–70,
January 7, 2000.
 b. Raffaghello, L. , Lee, C. , Safdie, F.M., Wei, M., Madia, F. , Gonidakis, S.
Bianchi, G. , and Longo V.D. Starvation-dependent Differential Stress
Resistance Protects Normal but not Cancer Cells Against High Dose
Oxidants/Chemotherapy. PNAS, 2008 Mar 3.
c.
Longo VD., Lieber, M., and Vijg, J. Turning Anti-aging genes against Cancer.
Nature Reviews Molecular Cell Biology, Nov. 2008, 902.

d. Safdie FM, Dorff T, Quinn D, Fontana L, Wei M, Lee C, Cohen P, Longo VD.
Fasting and Cancer Treatment in Humans. A case series report. Aging. 2009,
1(12): 988-1007

Tuesday, June 21: Diabetes and Cardiovascular Diseases- from the mechanisms of
pathogenesis, to standard treatment to anti-aging and regenerative medicine approaches
for prevention and treatment. Patient Case reports obtained from U of Genoa clinicians
will be assigned to students and discussed in class. The incidence of diabetes and
cardiovascular disease incidence in the last 30 years in the US will be compare to that in
Italy and the putative underlying causes will be discussed.

Readings: Type 2 diabetes and risk for functional decline and disability in older
persons. Volpato S, Maraldi C, Fellin R. Curr Diabetes Rev. 2010 May;6(3):134-
43. Review. Dietary interventions to extend life span and health span based on
calorie restriction. Minor RK, Allard JS, Younts CM, Ward TM, de Cabo R J
Gerontol A Biol Sci Med Sci. 2010 Jul;65(7):695-703. Epub 2010 Apr 6. Review

Wednesday, June 22: Stem cells, Regeneration and Bionics in the treatment and
prevention of diseases. A guest speaker from the Italian Institute of Technology Genoa
which specializes in robotics will present.

Readings:
a. Gass P, Riva MA 2007 CREB, neurogenesis and depression. Bioessays. 29:957-61.

b. Morgan D.2007 Amyloid, memory and neurogenesis. Exp Neurol. 205:330-5. Mar 14.

c. Yamasaki TR, et al 2007Neural stem cells improve memory in an inducible mouse model of
neuronal loss. J Neurosci. 27:11925-33.

d. Rando TA. 2006 Stem cells, ageing and the quest for immortality. Nature. 441:1080-6.

Thursday, June 23: Mediterranean Diet, exercise and lifestyle in Genova: How this port
city reached one of the highest over 65 population in the world (estimated at over 26%)
and how the City handles it. Lecture by a city health department official or U of Genoa
geriatrics professor.
Reading: Effectiveness of the Mediterranean diet in the elderly. Roman B, Carta
L, Martínez-González MA, Serra-Majem L. Clin Interv Aging. 2008;3(1):97-109.
Review
Friday, June 24

Final
Field Trip: Dinner in a Mediterranean diet restaurant in Genoa

Information on Field Trips

Field Trips

Several field trips will be included in the program. Both Drs. Villa and Longo will
participate in these trips.

1) Radiology Case Studies at the San Martino Hospital in Genoa

a) Description of San Martino Hospital

San Martino is a 500 year old hospital. It was founded in 1422. It is an organized,
well structured, and big complex in the city centre: a real city within the city of
Genoa. It is one of the biggest hospitals in Europe and 3,500 people work there. It is
one of the most renowned Italian medical centers for cardiology, cardiac surgery,
hematology, neurosurgery, neurology, and transplants.

b) Program
Students will observe and examine case studies, in particular case studies for
cancer, cardiovascular diseases, and Alzheimer. They will be also exposed to and
analyze the functioning of medical imaging equipment such as CAT SCAN and
MRI.

2) One day trip: Cinque Terre

The one day trip to the Cinque Terre will focus on hiking, movement, and the
Mediterranean diet.

a) Description of the Cinque Terre

Cinque Terre, which means Five Lands, comprise the five small coastal villages
Riomaggiore, Manarola, Corniglia, Vernazza, Monterosso located in the region
of Liguria, in the province of La Spezia. The Cinque Terre represent one of the best
preserved natural and semi-natural areas of the Mediterranean. The UNESCO in 1997
declared this area “World Human Heritage”.

The national Park and the Marine Reserve

The Cinque Terre became 1999 a National Park in order to protect an unique
environment made by a coast overhanging the sea with bays and small beaches,
thousands Kilometers of dry walls to mark the terraces for the wine-growing, typical
houses, medieval towns, sanctuaries, and panoramic footpaths overlooking the sea.
This territory was declared Protected Marine Area in 1999 to protect the numerous
sea fans and Posidonias forming deep grasslands that give shelter to innumerable
organisms and rare species. Moreover, for the presence of whales and dolphins these
waters are part of the Whales’ sanctuary. 

b) Hiking: The Lover’s Walk

The main attraction of the Cinque Terre is the landscape and the Cinque Terre boasts
some of the best coastline hiking trails in the world... Mediterranean herbs and trees
grow spontaneously from the top of the hills down to the water level. The path from
Riomaggiore to Manarola is called the Via Dell'Amore ("Lovers Walk"). The
beautiful trail along the shore is very easy to hike. It is carved into the rock; it
stretches along the coast overlooking the sea and arrives until the ancient sea town of
Manarola, whose picturesque harbor is sheltered by a golf closed by two crags.

c) Diet: Typical Products

The food of Cinque Terre preserves almost intact the characteristics of the ancient
times. Gastronomic delicacies from Cinque Terre which include pesto, fresh
vegetables, fish and olive oil.

d)Program:

- Arrival at Cinque Terre by boat and visit of the Cinque Terre by boat (For the
Cinque Terre Card see below)
- Morning: Hiking (Lover’s Trail) and Diet (Visit to the Sciacchetrà Museum in
Manarola)
- Lunch Break
- Afternoon: Food and Diet (Visit of the villages, of the ancient Oil Mill in Groppo,
the Virtual Aquarium, and the Anchovies Salting Centre in Monterosso)
e) The Cinque Terre Ferry Card

These cards provide the following services:

 Free use of ecological park buses and public elevators
 Free access to trekking path n° 2 (which includes "Lovers Lane”), the naturalistic
observation centers and recreation areas
 Free entrance to the Sciacchetrà Museum in Manarola, the History Museum in
Riomaggiore and the ancient Oil Mill in Groppo
 Free entrance to the Virtual Aquarium in Monterosso al Mare (currently closed
due to restoration) and the multimedia room in Levanto
 Free access to the Anchovies Salting Centre in Monterosso al Mare
 Three hours free bicycle hire (pending availability) for trails in the upper area of
the park
 A discount on products purchased at the Information Centres located throughout
the Cinque Terre Park
 A map of the walking paths (double format A4, with walking times and distances
of the paths)
 The Cinque Terre Card Battello also includes a ferry timetable and allows
unlimited ferry travel within the Marine Protected Area of the Cinque Terre. It also
allows unlimited train travel on the Levanto-La Spezia Centrale – Levanto line (on
Direct Regional and Interregional trains in 2° class).
 The Cinque Terre Card “Battello” is valid for 1 day only. 
 Price: 18-25 euros

3) Mediterranean Diet: One evening at a Ligurian Restaurant

One of the goals of our program is to gain a general knowledge about diets adopted
by very long-lived population from around the world and, in particular, from Liguria,
where we have one of the longest life expectancies in the planet. For this reason, we
will offer the students a dinner at a typical Ligurian restaurant. The students will be
able to have a first-hand experience of what they have been studying in class about
diets and the Mediterranean diet