A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan

被引：591

作者：

Brandhorst, Sebastian ^{[1
,2
]}

Choi, In Young ^{[1
,2
]}

Wei, Min ^{[1
,2
]}

Cheng, Chia Wei ^{[1
,2
]}

Sedrakyan, Sargis ^{[3
]}

Navarrete, Gerardo ^{[1
,2
]}

Dubeau, Louis ^{[4
]}

Yap, Li Peng ^{[5
]}

Park, Ryan ^{[5
]}

Vinciguerra, Manlio ^{[6
]}

Di Biase, Stefano ^{[1
,2
]}

Mirzaei, Hamed ^{[1
,2
]}

Mirisola, Mario G. ^{[7
]}

Childress, Patra ^{[8
]}

Ji, Lingyun ^{[9
]}

Groshen, Susan ^{[9
]}

Penna, Fabio ^{[10
]}

Odetti, Patrizio ^{[11
]}

Perin, Laura ^{[3
]}

Conti, Peter S. ^{[5
]}

Ikeno, Yuji ^{[12
]}

Kennedy, Brian K. ^{[13
]}

Cohen, Pinchas ^{[1
,2
]}

Morgan, Todd E. ^{[1
,2
]}

Dorff, Tanya B. ^{[14
]}

Longo, Valter D. ^{[1
,2
,15
]}

机构：

[1] Univ So Calif, Sch Gerontol, Longev Inst, Los Angeles, CA 90089 USA

[2] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA

[3] Univ So Calif, Saban Res Inst, Childrens Hosp Los Angeles, GOFARR Lab,Div Urol, Los Angeles, CA 90089 USA

[4] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90089 USA

[5] Univ So Calif, Keck Sch Med, Dept Radiol, Mol Imaging Ctr, Los Angeles, CA 90089 USA

[6] UCL, Royal Free Hosp, Inst Liver & Digest Hlth, Div Med, London NW3 2PF, England

[7] Univ Palermo, Dept Pathobiol & Med Biotechnol, I-90100 Palermo, Italy

[8] Univ So Calif, Keck Sch Med, Global Med Program, Los Angeles, CA 90089 USA

[9] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA

[10] Univ Turin, Dept Clin & Biol Sci, I-10100 Turin, Italy

[11] Univ Genoa, Dept Internal Med, I-16146 Genoa, Italy

[12] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst, Dept Pathol, San Antonio, TX 78229 USA

[13] Buck Inst Res Aging, Novato, CA 94945 USA

[14] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA

[15] FIRC Inst Mol Oncol, IFOM, I-20139 Milan, Italy

来源：

CELL METABOLISM | 2015年 / 22卷 / 01期

关键词：

LIFE-SPAN EXTENSION; ADULT HIPPOCAMPAL NEUROGENESIS; STEM-CELLS; MOLECULAR-MECHANISMS; STRESS RESISTANCE; GENETIC PATHWAYS; CANCER-CELLS; RESTRICTION; LONGEVITY; MODEL;

D O I：

10.1016/j.cmet.2015.05.012

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Prolonged fasting (PF) promotes stress resistance, but its effects on longevity are poorly understood. We show that alternating PF and nutrient-rich medium extended yeast lifespan independently of established pro-longevity genes. In mice, 4 days of a diet that mimics fasting (FMD), developed to minimize the burden of PF, decreased the size of multiple organs/systems, an effect followed upon re-feeding by an elevated number of progenitor and stem cells and regeneration. Bi-monthly FMD cycles started at middle age extended longevity, lowered visceral fat, reduced cancer incidence and skin lesions, rejuvenated the immune system, and retarded bone mineral density loss. In old mice, FMD cycles promoted hippocampal neurogenesis, lowered IGF-1 levels and PKA activity, elevated NeuroD1, and improved cognitive performance. In a pilot clinical trial, three FMD cycles decreased risk factors/biomarkers for aging, diabetes, cardiovascular disease, and cancer without major adverse effects, providing support for the use of FMDs to promote healthspan.

引用

页码：86 / 99

页数：14

共 68 条

[1] Comparative transcriptional pathway bioinformatic analysis of dietary restriction, Sir2, p53 and resveratrol life span extension in Drosophila
Antosh, Michael
Whitaker, Rachel
Kroll, Adam
Hosier, Suzanne
Chang, Chengyi
Bauer, Johannes
Cooper, Leon
Neretti, Nicola
Helfand, Stephen L.
[J]. CELL CYCLE, 2011, 10 (06) : 904 - 911
[2] SPATIAL-LEARNING AND MEMORY PROCESSES - THE SEARCH FOR THEIR NEUROBIOLOGICAL MECHANISMS IN THE RAT
BARNES, CA
[J]. TRENDS IN NEUROSCIENCES, 1988, 11 (04) : 163 - 169
[3] SOMATOTROPIC SIGNALING: TRADE-OFFS BETWEEN GROWTH, REPRODUCTIVE DEVELOPMENT, AND LONGEVITY
Bartke, Andrzej
Sun, Liou Y.
Longo, Valter
[J]. PHYSIOLOGICAL REVIEWS, 2013, 93 (02) : 571 - 598
[4] Aging of marrow stromal (skeletal) stem cells and their contribution to age-related bone loss
Bellantuono, Ilaria
Aldahmash, Abdullah
Kassem, Moustapha
[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2009, 1792 (04): : 364 - 370
[5] EFFECTS OF SCOPOLAMINE AND UNILATERAL LESIONS OF THE BASAL FOREBRAIN ON T-MAZE SPATIAL DISCRIMINATION AND ALTERNATION IN RATS
BENINGER, RJ
JHAMANDAS, K
BOEGMAN, RJ
ELDEFRAWY, SR
[J]. PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1986, 24 (05) : 1353 - 1360
[6] ROLE OF HIPPOCAMPAL NO IN THE ACQUISITION AND CONSOLIDATION OF INHIBITORY AVOIDANCE-LEARNING
BERNABEU, R
DESTEIN, ML
FIN, C
IZQUIERDO, I
MEDINA, JH
[J]. NEUROREPORT, 1995, 6 (11) : 1498 - 1500
[7] LONGEVITY, BODY-WEIGHT, AND NEOPLASIA IN AD LIBITUM-FED AND DIET-RESTRICTED C57BL6 MICE FED NIH-31 OPEN FORMULA DIET
BLACKWELL, BN
BUCCI, TJ
HART, RW
TURTURRO, A
[J]. TOXICOLOGIC PATHOLOGY, 1995, 23 (05) : 570 - 582
[8] Blagosklonny MV, 2009, AGING-US, V1, P1
[9] Short-term calorie and protein restriction provide partial protection from chemotoxicity but do not delay glioma progression
Brandhorst, Sebastian
Wei, Min
Hwang, Saewon
Morgan, Todd E.
Longo, Valter D.
[J]. EXPERIMENTAL GERONTOLOGY, 2013, 48 (10) : 1120 - 1128
[10] Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression
Cheng, Chia-Wei
Adams, Gregor B.
Perin, Laura
Wei, Min
Zhou, Xiaoying
Lam, Ben S.
Da Sacco, Stefano
Mirisola, Mario
Quinn, David I.
Dorff, Tanya B.
Kopchick, John J.
Longo, Valter D.
[J]. CELL STEM CELL, 2014, 14 (06) : 810 - 823

← 1 2 3 4 5 6 7 →