This document summarizes research on the potential anti-aging effects of the drug rapamycin. It describes a clinical trial that investigated the safety and impact of rapamycin supplementation in older adults. The trial found that rapamycin was generally safe and well-tolerated, with few adverse effects. It appeared to positively impact some measures of immune function and inflammation. However, the document notes that longer and larger studies are still needed to fully understand rapamycin's safety profile and ability to extend healthspan in humans.

1. “Come on, Doc! I’m
getting older! Is there
a pill for that?
Dean L. Kellogg, Jr., MD. Ph.D.
Departments of Medicine and Physiology
University of Texas Health Science Center
and
Geriatric Research, Education, and Clinical Center
Audie L. Murphy VA Hospital

2. The Aging and the Geriatric Population
A Wide Spectrum

3. The Aging and the Geriatric Population

4. www.livingto100.comGoal of
Anti-aging
Therapy…..
Make more
‘Successful
Agers’….with
a long and
healthy life!

5. PROVEN ‘Anti-aging’ Therapy:
Calorie Restriction extends
healthspan and lifespan

6. Calorie
restriction
retards
aging in
animals…
but is it
practical in
humans?

7. The Quest for ANTI-Aging Pills……
NIA’s Intervention Testing Program
PURPOSE:
To identify nutritional and pharmaceutical interventions
(already FDA approved) that could be safely employed
to extend the lifespan and healthspan of mice

8. •Curcumin
•Green tea extract
•Nitrofluorbiprofen
•4-hydroxy-phenylbutyl Nitrone
•Medium-chain triglyceride oil
•Oxaloacetic acid
•Resveratrol
•Methylene blue
•Simvastatin
Agents that did not extend lifespan in
laboratory animals

9. •Aspirin
•17αEstradiol
•NGDA (nordihydroguaiaretic acid)
•Protandim
Agents that extend lifespan in male but
not female laboratory animals

10. •Acarbose-greater effect in males with small
effect in females-but had to be started in youth
•Rapamycin-greater effect in females-could be
started on ‘old’ mice’
2 Agents that extend lifespan in both
MALE and FEMALE laboratory
animals

11. RAPAMYCIN…a weird drug from a
weird place….Easter Island=Rapa Nui

12. Moai

13. Moai
Dig into the soil of
Rapa Nui and find
that there is more
than meets the eye!
RAPAMYCIN
(Sirolimus)

14. ITP: Mice on Rapamycin are “Younger”
in activity levels and coat appearance
Control Female RAPA Female
Control Male RAPA Male
ALL
Dead
9-14%
Lifespan
increase
Activity level
maintained in
males
RAPA effects
observed if
started late in
life

15. FDA Approved Uses Of
Rapamycin in Humans
• Rapamycin is FDA approved for use as an
immunosuppressive drug in preventing transplant rejection,
with drug eluting stents to limit coronary artery re-stenosis,
and for lymphangioleiomyomatosis.
• Rapalogs (drugs like rapamycin) are FDA approved for use
as cancer treatments.
• Most human studies of RAPA involved transplant patients
who take a combination of immunosuppressive drugs thus
interpretation of RAPA safety and effects are difficult.

16. Anti-aging Use of Rapamycin in
Healthy Humans
(Science, News & Analysis, 2013)
• Some researchers say NO.
• “Rapamycin leads to insulin resistance—a precursor of diabetes—in
mice and humans, and transplant recipients have developed
diabetes.”
• “I’d be very hesitant to be a participant” in a clinical trial, Miller
says.
• Some researchers say YES.
• “We don’t have a huge body of evidence of its effects in a healthy
older adult.”
IS RAPAMYCIN SAFE TO GIVE TO HEALTHY OLDER
PERSONS?

17. Inclusion Criteria
-Subjects all in good health with all chronic diseases
(hypertension, coronary artery disease, etc.)
clinically stable.
-AGE 80-95 (Phase 1)
-AGE 70-95 (Phase 2)
•Participants on therapy (either Rapamycin 1mg qD or
placebo) for the 4 months (Phase 1) or 2 months (Phase 2).
•Added RAPA or placebo to other medications subjects
were already taking
Study Design

18. Assessment of Rapamycin SAFETY
• Physical examinations
• Clinical blood work
• Urinalysis
• Oral Glucose Tolerance Tests
• EKG
• Self-reported side-effects
• Pts called on weekly basis

19. IMMUNOLOGICAL TESTS
Rapa improved antibody responses in older mice!
– PHASE 1 -Tests on Immunity
• Hepatitis B naïve participants are immunized with the hepatitis B
vaccine. Humoral (antibody titer) and cellular (T cell proliferation)
responses are assessed.
– PHASE 2 -Tests on Immunity
• Participants are immunized with the Flu vaccine. Humoral (antibody
titer) and cellular (T cell proliferation) responses are assessed.
– Tests on Inflammation
• Immune parameters characteristically altered by aging are
assessed. These include: i) serum cytokine levels; ii) variety of
white blood cell (B cell and T cells) studies.

20. PHYSICAL PERFORMANCE
TESTS
• Hand Grip (3 trials hand dynamometer-Lt and Rt)
• Timed Walk (3 trials-40 feet)

21. COGNITIVE TESTS
• EXIT (Executive Interview 25-which
includes letter fluency)
• SLUMS (St. Louis University Mental Status
exam) includes memory test, digit span, and
animal fluency
• TAPS (Texas Assessment of Processing
Speed) a digit/symbol coding test available
in alternate forms to eliminate learning
effects

22. 28 Subjects-Ages, Sex, and Final Rapamycin Levels

23. A B C
D E F
G H I
J K L
Pre Post Pre Post
PLACEBO RAPA
4.8
4.4
4.0
3.6
Albumin
Serumconcentration(g/dL)
Pre Post Pre Post
PLACEBO RAPA
4.8
4.4
4.0
3.6
Albumin
Serumconcentration(g/dL)
Weight
Weight(kg)
Pre Post Pre Post
PLACEBO RAPA
70
80
90
100
110
Weight
Weight(kg)
Pre Post Pre Post
PLACEBO RAPA
70
80
90
100
110
White blood cell count
WBCx103/μl
Pre Post Pre Post
PLACEBO RAPA
4
5
6
7
White blood cell count
WBCx103/μl
Pre Post Pre Post
PLACEBO RAPA
4
5
6
7
300
200
100
Triglycerides
Triglyceridesinserum(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
300
200
100
Triglycerides
Triglyceridesinserum(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
Low density lipoprotein
LDLconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
75
100
125
150
Low density lipoprotein
LDLconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
75
100
125
150
High density lipoprotein
HDLserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
30
50
70
High density lipoprotein
HDLserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
30
50
70
Serum protein
Serumprotein(g/dL)
Pre Post Pre Post
PLACEBO RAPA
6.5
7.0
7.5
Serum protein
Serumprotein(g/dL)
Pre Post Pre Post
PLACEBO RAPA
6.5
7.0
7.5
Hemoglobin A1c
HgbA1c(percent)
Pre Post Pre Post
PLACEBO RAPA
5.0
5.5
6.0
6.5
Hemoglobin A1c
HgbA1c(percent)
Pre Post Pre Post
PLACEBO RAPA
5.0
5.5
6.0
6.5
Platelets
Pre Post Pre Post
PLACEBO RAPA
150
200
250
Plateletsx103/μl
Platelets
Pre Post Pre Post
PLACEBO RAPA
150
200
250
Plateletsx103/μl
Calcium
Calciumserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
9.0
9.5
10.0
Calcium
Calciumserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
9.0
9.5
10.0
Hematocrit
Hematocrit(%)
Pre Post Pre Post
PLACEBO RAPA
35
40
45
Hematocrit
Hematocrit(%)
Pre Post Pre Post
PLACEBO RAPA
35
40
45
120
110
100
90
80
Fasting blood glucose
Glucoseserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
120
110
100
90
80
Fasting blood glucose
Glucoseserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
A B C
D E F
G H I
J K L
Pre Post Pre Post
PLACEBO RAPA
4.8
4.4
4.0
3.6
Albumin
Serumconcentration(g/dL)
Pre Post Pre Post
PLACEBO RAPA
4.8
4.4
4.0
3.6
Albumin
Serumconcentration(g/dL)
Weight
Weight(kg)
Pre Post Pre Post
PLACEBO RAPA
70
80
90
100
110
Weight
Weight(kg)
Pre Post Pre Post
PLACEBO RAPA
70
80
90
100
110
White blood cell count
WBCx103/μl
Pre Post Pre Post
PLACEBO RAPA
4
5
6
7
White blood cell count
WBCx103/μl
Pre Post Pre Post
PLACEBO RAPA
4
5
6
7
300
200
100
Triglycerides
Triglyceridesinserum(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
300
200
100
Triglycerides
Triglyceridesinserum(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
Low density lipoprotein
LDLconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
75
100
125
150
Low density lipoprotein
LDLconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
75
100
125
150
High density lipoprotein
HDLserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
30
50
70
High density lipoprotein
HDLserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
30
50
70
Serum protein
Serumprotein(g/dL)
Pre Post Pre Post
PLACEBO RAPA
6.5
7.0
7.5
Serum protein
Serumprotein(g/dL)
Pre Post Pre Post
PLACEBO RAPA
6.5
7.0
7.5
Hemoglobin A1c
HgbA1c(percent)
Pre Post Pre Post
PLACEBO RAPA
5.0
5.5
6.0
6.5
Hemoglobin A1c
HgbA1c(percent)
Pre Post Pre Post
PLACEBO RAPA
5.0
5.5
6.0
6.5
Platelets
Pre Post Pre Post
PLACEBO RAPA
150
200
250
Plateletsx103/μl
Platelets
Pre Post Pre Post
PLACEBO RAPA
150
200
250
Plateletsx103/μl
Calcium
Calciumserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
9.0
9.5
10.0
Calcium
Calciumserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
9.0
9.5
10.0
Hematocrit
Hematocrit(%)
Pre Post Pre Post
PLACEBO RAPA
35
40
45
Hematocrit
Hematocrit(%)
Pre Post Pre Post
PLACEBO RAPA
35
40
45
120
110
100
90
80
Fasting blood glucose
Glucoseserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
120
110
100
90
80
Fasting blood glucose
Glucoseserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
CLINICAL
LAB TEST
RESULTS:
Blood chemistry
and Red Blood
Cells
•Reduced H/H
and indices within
RAPA and
between Groups

24. METABOLIC
TEST (OGTT)
RESULTS
•No differences in
insulin sensitivity

25. White Blood
Cells
30
CD4+ T cells
PLACEBO RAPA
%ofCD3+Tcells
Ratio CD4+/CD8+
PLACEBO RAPA
%ofnaïveCD4+cells
PLACEBO RAPA PLACEBO RAPA
%ofCD4+cells
%ofmemoryCD4+cells
TREG cells (CD4+foxp3+)
PLACEBO RAPA
%ofCD4+parentpopulation
0 6 0 6
0
5
10
15
20
0 6 0 6
0
20
40
60
80
100
Naïve CD4+ (RA+RO-)
PLACEBO RAPA
%ofCD4+cells
0 6 0 6
0
20
40
60
80
Memory CD4+ (RA-RO+) Memory CD4+ PD1+
0 6 0 6
0
20
40
60
80
100
0 6 0 6
0
5
10
15
20
0 6 0 6
0
20
40
60
G H I
J K L
30
CD4+ T cells
PLACEBO RAPA
%ofCD3+Tcells
Ratio CD4+/CD8+
PLACEBO RAPA
%ofnaïveCD4+cells
PLACEBO RAPA PLACEBO RAPA
%ofCD4+cells
%ofmemoryCD4+cells
TREG cells (CD4+foxp3+)
PLACEBO RAPA
%ofCD4+parentpopulation
0 6 0 6
0
5
10
15
20
PLACEBO RAPA
%ofCD4+parentpopulation
0 6 0 6
0
5
10
15
20
0 6 0 6
0
20
40
60
80
100
Naïve CD4+ (RA+RO-)
PLACEBO RAPA
%ofCD4+cells
0 6 0 6
0
20
40
60
80
Memory CD4+ (RA-RO+) Memory CD4+ PD1+
0 6 0 6
0
20
40
60
80
100
0 6 0 6
0
5
10
15
20
0 6 0 6
0
20
40
60
G H I
J K L
CD8+ T cells
PLACEBO RAPA
%ofCD3+Tcells
Memory CD8+ (RA-RO+)
Naïve CD8+ PD1+
PLACEBO RAPA
PLACEBO RAPA PLACEBO RAPAPLACEBO RAPA
Naïve CD8+ (RA+RO-)
PLACEBO RAPA
%ofCD8+cells
Memory CD8+ CD28+ Memory CD8+ PD1+
%ofnaïveCD8+cells
%ofmemoryCD8+
%ofmemoryCD8+
%ofCD8+cells
0 6 0 6
0
10
20
30
0 6 0 6
0
20
40
60
80
100
0 6 0 6
0
10
20
30
40
50
0 6 0 6
0
10
20
30
40
50
0 6 0 6
0
20
40
60
80
100
0 6 0 6
0
20
40
60
80
100
M N O
P Q R
CD8+ T cells
PLACEBO RAPA
%ofCD3+Tcells
Memory CD8+ (RA-RO+)
Naïve CD8+ PD1+
PLACEBO RAPA
PLACEBO RAPA PLACEBO RAPAPLACEBO RAPA
Naïve CD8+ (RA+RO-)
PLACEBO RAPA
%ofCD8+cells
Memory CD8+ CD28+ Memory CD8+ PD1+
%ofnaïveCD8+cells
%ofmemoryCD8+
%ofmemoryCD8+
%ofCD8+cells
0 6 0 6
0
10
20
30
0 6 0 6
0
20
40
60
80
100
0 6 0 6
0
10
20
30
40
50
0 6 0 6
0
10
20
30
40
50
0 6 0 6
0
20
40
60
80
100
0 6 0 6
0
20
40
60
80
100
M N O
P Q R
0 6 0 6
0
10
20
30
B cells (CD20+)
PLACEBO RAPA
%ofsinglets
T cells (CD3+)
PLACEBO RAPA
Myeloid lineage (CD11b+)
PLACEBO RAPA
Myeloid P1 subset Myeloid P2 subset Myeloid P3 subset
PLACEBO RAPA
%ofCD11b+
0 6 0 6
0
10
20
30
%ofCD20-parentpopulation
0 6 0 6
0
10
20
30
%ofCD20-parentpopulation
0 6 0 6
50
60
70
80
90
100
PLACEBO RAPA PLACEBO RAPA
%ofCD11b+
%ofCD11b+
0 6 0 6
0
10
20
30
40
0 6 0 6
0
5
10
15
20
A B C
D E F
0 6 0 6
0
10
20
30
B cells (CD20+)
PLACEBO RAPA
%ofsinglets
T cells (CD3+)
PLACEBO RAPA
Myeloid lineage (CD11b+)
PLACEBO RAPA
Myeloid P1 subset Myeloid P2 subset Myeloid P3 subset
PLACEBO RAPA
%ofCD11b+
0 6 0 6
0
10
20
30
%ofCD20-parentpopulation
0 6 0 6
0
10
20
30
%ofCD20-parentpopulation
0 6 0 6
50
60
70
80
90
100
PLACEBO RAPA PLACEBO RAPA
%ofCD11b+
%ofCD11b+
0 6 0 6
0
10
20
30
40
0 6 0 6
0
5
10
15
20
A B C
D E F
•No differences

26. Cytokines
(Inflammatory
Mediators)
IL-13
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.87
0
200
400
600
IL-15
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.19
0
5
10
15
20
IL-17A
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml p = 0.31
0
10
20
30
IL-6 (ELISA)
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.09
0
5
10
15
20
VEGF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.36
0
200
400
600
800
TNF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.63
0
200
400
600
MIP-1
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.95
0
10
20
30
40
50
MIP-1
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.85
0
50
100
150
IL-8
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.11
0
20
40
60
IL-10
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.19
0
10
20
30
IL-12p40
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.26
0
10
20
30
IL-12p70
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.25
0
10
20
30
40
50
IL-4
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.61
0
20
40
60
80
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.04
TNF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
0
10
20
30
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml 0
50
100
150
200
250
IL-1
p = >0.99
IL-1
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.02
0
5
10
15
20
MCP-1
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.73
0
500
1000
1500
IFN2
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.65
0
50
100
150
IFN
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.26
0
50
100
150
IP-10
p = 0.77
0
500
1000
1500
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.90
0
100
200
300
400
EGF Eotaxin
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.50
0
200
400
600
800
G-CSF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.14
0
50
100
150
GMCSF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.44
0
20
40
60
80
100
A B C D
E F G H
I J K L
M N O P
Q R S T
U V W XIL-13
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.87
0
200
400
600
IL-13
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.87
0
200
400
600
IL-15
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.19
0
5
10
15
20
IL-15
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.19
0
5
10
15
20
IL-17A
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml p = 0.31
0
10
20
30
IL-17A
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml p = 0.31
0
10
20
30
IL-6 (ELISA)
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.09
0
5
10
15
20
IL-6 (ELISA)
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.09
0
5
10
15
20
VEGF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.36
0
200
400
600
800
VEGF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.36
0
200
400
600
800
TNF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.63
0
200
400
600
TNF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.63
0
200
400
600
MIP-1
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.95
0
10
20
30
40
50
MIP-1
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.95
0
10
20
30
40
50
MIP-1
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.85
0
50
100
150
MIP-1
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.85
0
50
100
150
IL-8
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.11
0
20
40
60
IL-8
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.11
0
20
40
60
IL-10
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.19
0
10
20
30
IL-10
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.19
0
10
20
30
IL-12p40
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.26
0
10
20
30
IL-12p40
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.26
0
10
20
30
IL-12p70
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.25
0
10
20
30
40
50
IL-12p70
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.25
0
10
20
30
40
50
IL-4
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.61
0
20
40
60
80
IL-4
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.61
0
20
40
60
80
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.04
TNF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
0
10
20
30
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.04
TNF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
0
10
20
30
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml 0
50
100
150
200
250
IL-1
p = >0.99
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml 0
50
100
150
200
250
IL-1
p = >0.99
IL-1
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.02
0
5
10
15
20
IL-1
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.02
0
5
10
15
20
MCP-1
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.73
0
500
1000
1500
MCP-1
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.73
0
500
1000
1500
IFN2
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.65
0
50
100
150
IFN2
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.65
0
50
100
150
IFN
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.26
0
50
100
150
IFN
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.26
0
50
100
150
IP-10
p = 0.77
0
500
1000
1500
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
IP-10
p = 0.77
0
500
1000
1500
0
500
1000
1500
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.90
0
100
200
300
400
EGF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.90
0
100
200
300
400
EGF Eotaxin
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.50
0
200
400
600
800
Eotaxin
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.50
0
200
400
600
800
G-CSF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.14
0
50
100
150
G-CSF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.14
0
50
100
150
GMCSF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.44
0
20
40
60
80
100
GMCSF
0 wks 6 wks 0 wks 6 wks
PLACEBO RAPA
pg/ml
p = 0.44
0
20
40
60
80
100
A B C D
E F G H
I J K L
M N O P
Q R S T
U V W X
•No differences

27. Other Results?
•No statistically significant differences in immunization,
physical performance, cognitive testing

28. ANY Beneficial Results?
•Reduced weight (1.1#) in RAPA group while placebo
group gained (0.5#)

29. Subject and Family Comments
- “I couldn’t tell I was taking anything different.”
-“We saw a slight increase in his cognitive and memory
abilities on the med. Not marked but a very slight
increase.”
- “His overall disposition seemed better.”
-“He was more frisky on the rapamycin…..can you give
him some more?”

30. POSSIBLE ADVERSE REACTIONS
• Stomatitis (2 pts-1 Rapa and 1 placebo-resolved so
continued participation)
• Diarrhea (2 pts-ended participation)
• Acneform Facial Rash (1 pt-ended participation)
ALL POTENTIAL ADVERSE REACTIONS PREVIOUSLY
REPORTED IN TRANSPLANT PATIENTS

31. A Randomized Control Trial to Establish the Feasibility and Safety
of Rapamycin Treatment in an
Older Human Cohort: Immunological, Physical Performance, and
Cognitive Effects
Ellen Kraiga,b,*, Leslie A. Linehanb, Hanyu Lianga, Terry Q. Romoa,g, Qianqian Liuc,
Yubo Wue, Adriana D. Benavidesd, Tyler J. Curiela,e, Martin A. Javorsa,f, Nicolas Musia,e,g,
Laura Chiodog, Wouter Koekb,f, Jonathan A.L. Gelfonda,c, and Dean L. Kellogg, Jr.a,e,g
CONCLUSION:
Rapamycin is just as safe to use in healthy
older persons as transplant patients….but
what about benefits?

32. Possible Rapamycin Benefits?

33. The Search for Rapamycin Benefits:
Cardiovascular Effects in 70+yo Persons
Initial Results:
IMPROVED CARDIAC
FUNCTION?
Measured by cardiac MRI
in 6 older persons
pre post
0
50
100
150
Flow: Transmitral Total Volume
ml
p = 0.0211
paired, parametric
41
42-no data
43
44
45
46

34. Successful Aging to All!

35. THANKS
• CTSA
• SA Pepper Center
• Dr. Ellen Kraig
• Terry Romo
• Leslie Linehan
• Beth Wu
• Darcy Bair-Kelps
• Che Kelly