Calorie restriction (CR) has been studied as a way to prolong longevity, and CR before chemotherapy can reduce hematological toxicity in cancer patients. We investigated the influence of fasting on immune cells and immature hematopoietic cells. In fasted mice, there was a significant reduction in the hematopoietic stem cell count but no significant difference for progenitor cells. Colony assays showed no difference and the rates of early and late apoptosis were almost identical when comparing fasted and control mice. DNA cell cycle analysis of immature bone marrow (BM) cells showed that CR caused a significant increase in the percentage in the G0/G1 phase and decreases in the S and G2/M phases. We detected a remarkable increase of T cells in the BM of fasted mice. CD44– naïve CD8+ T cells were more numerous in fasted BM, as were naïve CD4+ T cells, and part of those T cells showed less tendency in the G0/G1 phase. Immature hematopoietic cells remained in a relatively quiescent state and retention of colony-forming capacity during CR. The number of naïve T cells in the BM of fasted mice increased. These findings imply immature hematopoietic cells and some lymphoid cells can survive starvation, whilst maintaining their function.

1.
McCay
CM
,
Crowell
MF
,
Maynard
LA
.
The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935
.
Nutrition
.
1989
May-Jun
;
5
(
3
):
155
71
.
[PubMed]
0899-9007
2.
Goodrick
CL
,
Ingram
DK
,
Reynolds
MA
,
Freeman
JR
,
Cider
N
.
Effects of intermittent feeding upon body weight and lifespan in inbred mice: interaction of genotype and age
.
Mech Ageing Dev
.
1990
Jul
;
55
(
1
):
69
87
.
[PubMed]
0047-6374
3.
Payne
AM
,
Dodd
SL
,
Leeuwenburgh
C
.
Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space
.
J Appl Physiol (1985)
.
2003
Dec
;
95
(
6
):
2554
62
.
[PubMed]
8750-7587
4.
Skorupa
DA
,
Dervisefendic
A
,
Zwiener
J
,
Pletcher
SD
.
Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster
.
Aging Cell
.
2008
Aug
;
7
(
4
):
478
90
.
[PubMed]
1474-9718
5.
Greer
EL
,
Brunet
A
.
Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans
.
Aging Cell
.
2009
Apr
;
8
(
2
):
113
27
.
[PubMed]
1474-9718
6.
Jiang
JC
,
Jaruga
E
,
Repnevskaya
MV
,
Jazwinski
SM
.
An intervention resembling caloric restriction prolongs life span and retards aging in yeast
.
FASEB J
.
2000
Nov
;
14
(
14
):
2135
7
.
[PubMed]
0892-6638
7.
Lin
SJ
,
Kaeberlein
M
,
Andalis
AA
,
Sturtz
LA
,
Defossez
PA
,
Culotta
VC
, et al.
Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration
.
Nature
.
2002
Jul
;
418
(
6895
):
344
8
.
[PubMed]
0028-0836
8.
Valenzano
DR
,
Terzibasi
E
,
Genade
T
,
Cattaneo
A
,
Domenici
L
,
Cellerino
A
.
Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate
.
Curr Biol
.
2006
Feb
;
16
(
3
):
296
300
.
[PubMed]
0960-9822
9.
Kemnitz
JW
.
Calorie restriction and aging in nonhuman primates
.
ILAR J
.
2011
;
52
(
1
):
66
77
.
[PubMed]
1084-2020
10.
Colman
RJ
,
Anderson
RM
,
Johnson
SC
,
Kastman
EK
,
Kosmatka
KJ
,
Beasley
TM
, et al.
Caloric restriction delays disease onset and mortality in rhesus monkeys
.
Science
.
2009
Jul
;
325
(
5937
):
201
4
.
[PubMed]
0036-8075
11.
Colman
RJ
,
Beasley
TM
,
Kemnitz
JW
,
Johnson
SC
,
Weindruch
R
,
Anderson
RM
.
Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys
.
Nat Commun
.
2014
Apr
;
5
(
1
):
3557
.
[PubMed]
2041-1723
12.
Mattison
JA
,
Roth
GS
,
Beasley
TM
,
Tilmont
EM
,
Handy
AM
,
Herbert
RL
, et al.
Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study
.
Nature
.
2012
Sep
;
489
(
7415
):
318
21
.
[PubMed]
0028-0836
13.
Fontana
L
,
Partridge
L
.
Promoting health and longevity through diet: from model organisms to humans
.
Cell
.
2015
Mar
;
161
(
1
):
106
18
.
[PubMed]
0092-8674
14.
Raffaghello
L
,
Lee
C
,
Safdie
FM
,
Wei
M
,
Madia
F
,
Bianchi
G
, et al.
Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy
.
Proc Natl Acad Sci USA
.
2008
Jun
;
105
(
24
):
8215
20
.
[PubMed]
0027-8424
15.
Safdie
FM
,
Dorff
T
,
Quinn
D
,
Fontana
L
,
Wei
M
,
Lee
C
, et al.
Fasting and cancer treatment in humans: A case series report
.
Aging (Albany NY)
.
2009
Dec
;
1
(
12
):
988
1007
.
[PubMed]
1945-4589
16.
de Groot
S
,
Vreeswijk
MP
,
Welters
MJ
,
Gravesteijn
G
,
Boei
JJ
,
Jochems
A
, et al.
The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study
.
BMC Cancer
.
2015
Oct
;
15
(
1
):
652
.
[PubMed]
1471-2407
17.
Okada
S
,
Nakauchi
H
,
Nagayoshi
K
,
Nishikawa
S
,
Miura
Y
,
Suda
T
.
In vivo and in vitro stem cell function of c-kit- and Sca-1-positive murine hematopoietic cells
.
Blood
.
1992
Dec
;
80
(
12
):
3044
50
.
[PubMed]
0006-4971
18.
Shushimita
S
,
de Bruijn
MJ
,
de Bruin
RW
,
IJzermans
JN
,
Hendriks
RW
,
Dor
FJ
.
Dietary restriction and fasting arrest B and T cell development and increase mature B and T cell numbers in bone marrow
.
PLoS One
.
2014
Feb
;
9
(
2
):
e87772
.
[PubMed]
1932-6203
19.
Chen
J
,
Astle
CM
,
Harrison
DE
.
Delayed immune aging in diet-restricted B6CBAT6 F1 mice is associated with preservation of naive T cells
.
J Gerontol A Biol Sci Med Sci
.
1998
Sep
;
53
(
5
):
B330
7
.
[PubMed]
1079-5006
20.
Fujita
Y
,
Murakami
M
,
Ogawa
Y
,
Masuzaki
H
,
Tanaka
M
,
Ozaki
S
, et al.
Leptin inhibits stress-induced apoptosis of T lymphocytes
.
Clin Exp Immunol
.
2002
Apr
;
128
(
1
):
21
6
.
[PubMed]
0009-9104
21.
Muraoka
T
,
Shirouzu
K
,
Ozasa
H
,
Oka
Y
,
Momosaki
K
,
Iwakuma
N
, et al.
The effect of starvation on blood stream cancer cell metastasis to the liver in rat after laparotomy
.
Kurume Med J
.
2013
;
60
(
2
):
59
66
.
[PubMed]
0023-5679
22.
Tanaka
M
,
Suganami
T
,
Kim-Saijo
M
,
Toda
C
,
Tsuiji
M
,
Ochi
K
, et al.
Role of central leptin signaling in the starvation-induced alteration of B-cell development
.
J Neurosci
.
2011
Jun
;
31
(
23
):
8373
80
.
[PubMed]
0270-6474
23.
Zhang
S
,
Readinger
JA
,
DuBois
W
,
Janka-Junttila
M
,
Robinson
R
,
Pruitt
M
, et al.
Constitutive reductions in mTOR alter cell size, immune cell development, and antibody production
.
Blood
.
2011
Jan
;
117
(
4
):
1228
38
.
[PubMed]
0006-4971
24.
Messaoudi
I
,
Warner
J
,
Fischer
M
,
Park
B
,
Hill
B
,
Mattison
J
, et al.;
Messaoudi I1
.
Warner J, Fischer M, Park B, Hill B, Mattison J, Lane MA, Roth GS, Ingram DK, Picker LJ, Douek DC, Mori M, Nikolich-Zugich J. Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates
.
Proc Natl Acad Sci USA
.
2006
;
103
(
51
):
19448
53
. 0027-8424
25.
Mazo
IB
,
Honczarenko
M
,
Leung
H
,
Cavanagh
LL
,
Bonasio
R
,
Weninger
W
, et al.
Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells
.
Immunity
.
2005
Feb
;
22
(
2
):
259
70
.
[PubMed]
1074-7613
26.
Tokoyoda
K
,
Zehentmeier
S
,
Hegazy
AN
,
Albrecht
I
,
Grün
JR
,
Löhning
M
, et al.
Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow
.
Immunity
.
2009
May
;
30
(
5
):
721
30
.
[PubMed]
1074-7613
27.
Maekawa
Y
,
Ishifune
C
,
Tsukumo
S
,
Hozumi
K
,
Yagita
H
,
Yasutomo
K
.
Notch controls the survival of memory CD4+ T cells by regulating glucose uptake
.
Nat Med
.
2015
Jan
;
21
(
1
):
55
61
.
[PubMed]
1078-8956
28.
Becker
TC
,
Coley
SM
,
Wherry
EJ
,
Ahmed
R
.
Bone marrow is a preferred site for homeostatic proliferation of memory CD8 T cells
.
J Immunol
.
2005
Feb
;
174
(
3
):
1269
73
.
[PubMed]
0022-1767
29.
Di Biase
S
,
Lee
C
,
Brandhorst
S
,
Manes
B
,
Buono
R
,
Cheng
CW
, et al.
Fasting-mimicking diet reduces HO-1 to promote T cell-mediated tumor cytotoxicity
.
Cancer Cell
.
2016
Jul
;
30
(
1
):
136
46
.
[PubMed]
1535-6108
30.
Lu
Z
,
Xie
J
,
Wu
G
,
Shen
J
,
Collins
R
,
Chen
W
, et al.
Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation
.
Nat Med
.
2017
Jan
;
23
(
1
):
79
90
.
[PubMed]
1078-8956
31.
Chen
J
,
Astle
CM
,
Harrison
DE
.
Hematopoietic senescence is postponed and hematopoietic stem cell function is enhanced by dietary restriction
.
Exp Hematol
.
2003
Nov
;
31
(
11
):
1097
103
.
[PubMed]
0301-472X
32.
Tang
D
,
Tao
S
,
Chen
Z
,
Koliesnik
IO
,
Calmes
PG
,
Hoerr
V
, et al.
Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging
.
J Exp Med
.
2016
Apr
;
213
(
4
):
535
53
.
[PubMed]
0022-1007
33.
Jensen
TL
,
Kiersgaard
MK
,
Sørensen
DB
,
Mikkelsen
LF
.
Fasting of mice: a review
.
Lab Anim
.
2013
Oct
;
47
(
4
):
225
40
.
[PubMed]
0023-6772
34.
Cheng
CW
,
Adams
GB
,
Perin
L
,
Wei
M
,
Zhou
X
,
Lam
BS
, et al.
Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression
.
Cell Stem Cell
.
2014
Jun
;
14
(
6
):
810
23
.
[PubMed]
1934-5909
35.
Doyle
C
,
Kushi
LH
,
Byers
T
,
Courneya
KS
,
Demark-Wahnefried
W
,
Grant
B
, et al.;
2006 Nutrition, Physical Activity and Cancer Survivorship Advisory Committee
;
American Cancer Society
.
Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices
.
CA Cancer J Clin
.
2006
Nov-Dec
;
56
(
6
):
323
53
.
[PubMed]
0007-9235
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