Abstract
Metformin is sometimes proposed to be an “anti-aging” drug, based on preclinical experiments with lower-order organisms and numerous retrospective data on beneficial health outcomes for type 2 diabetics. Large prospective, placebo-controlled trials are planned, in pilot stage or running, to find a new use (or indication) for an aging population. As one of the metformin trials has “frailty” as its endpoint, similar to a trial with a plant-derived senolytic, the latter class of novel anti-aging drugs is briefly discussed. Concerns exist not only for vitamin B12 and B6 deficiencies, but also about whether there are adverse effects of metformin on individuals who try to remain healthy by maintaining cardiovascular fitness via exercise.
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References
1.
de Magalhães
JP
, Stevens
M
, Thornton
D
. The Business of Anti-Aging Science
. Trends Biotechnol
. 2017
Nov
;35
(11
):1062
–73
.
[PubMed]
0167-77993.
Soria-Valles
C
, Osorio
FG
, Gutiérrez-Fernández
A
, De Los Angeles
A
, Bueno
C
, Menéndez
P
, et al.. NF-κB activation impairs somatic cell reprogramming in ageing
. Nat Cell Biol
. 2015
Aug
;17
(8
):1004
–13
.
[PubMed]
1465-73924.
Osorio
FG
, Bárcena
C
, Soria-Valles
C
, Ramsay
AJ
, de Carlos
F
, Cobo
J
, et al.. Nuclear lamina defects cause ATM-dependent NF-κB activation and link accelerated aging to a systemic inflammatory response
. Genes Dev
. 2012
Oct
;26
(20
):2311
–24
.
[PubMed]
0890-93695.
Soria-Valles
C
, Osorio
FG
, Gutiérrez-Fernández
A
, De Los Angeles
A
, Bueno
C
, Menéndez
P
, et al.. Retraction Note: NF-κB activation impairs somatic cell reprogramming in ageing
. Nat Cell Biol
. 2019
Mar
;21
(3
):410
.
[PubMed]
1465-73926.
Harrison
DE
, Strong
R
, Sharp
ZD
, Nelson
JF
, Astle
CM
, Flurkey
K
, et al.. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
. Nature
. 2009
Jul
;460
(7253
):392
–5
.
[PubMed]
0028-08367.
Kaeberlein
M
, Kennedy
BK
. Ageing: A midlife longevity drug
. Nature
. 2009
Jul
;460
(7253
):331
–2
.
[PubMed]
0028-08368.
Walters
HE
, Cox
LS
. mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases
. Int J Mol Sci
. 2018
Aug
;19
(8
):E2325
.
[PubMed]
1661-65969.
Kaeberlein
M
, Galvan
V
. Rapamycin and Alzheimer’s disease: time for a clinical trial
. Sci Transl Med
. 2019
Jan
;11
(476
):eaar4289
.
[PubMed]
1946-623410.
Chang
J
, Wang
Y
, Shao
L
, Laberge
RM
, Demaria
M
, Campisi
J
, et al.. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
. Nat Med
. 2016
Jan
;22
(1
):78
–83
.
[PubMed]
1078-895611.
van Deursen
JM
. The role of senescent cells in ageing
. Nature
. 2014
May
;509
(7501
):439
–46
.
[PubMed]
0028-083612.
Childs
BG
, Gluscevic
M
, Baker
DJ
, Laberge
RM
, Marquess
D
, Dananberg
J
, et al.. Senescent cells: an emerging target for diseases of ageing
. Nat Rev Drug Discov
. 2017
Oct
;16
(10
):718
–35
.
[PubMed]
1474-177613.
Kirkland
JL
, Tchkonia
T
, Zhu
Y
, Niedernhofer
LJ
, Robbins
PD
. The Clinical Potential of Senolytic Drugs
. J Am Geriatr Soc
. 2017
Oct
;65
(10
):2297
–301
.
[PubMed]
0002-861414.
Xu
M
, Pirtskhalava
T
, Farr
JN
, Weigand
BM
, Palmer
AK
, Weivoda
MM
, et al.. Senolytics improve physical function and increase lifespan in old age
. Nat Med
. 2018
Aug
;24
(8
):1246
–56
.
[PubMed]
1078-895615.
Myrianthopoulos
V
. The emerging field of senotherapeutic drugs
. Future Med Chem
. 2018
Oct
;10
(20
):2369
–72
.
[PubMed]
1756-891916.
Zhu
Y
, Tchkonia
T
, Pirtskhalava
T
, Gower
AC
, Ding
H
, Giorgadze
N
, et al.. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs
. Aging Cell
. 2015
Aug
;14
(4
):644
–58
.
[PubMed]
1474-971817.
Fuhrmann-Stroissnigg
H
, Ling
YY
, Zhao
J
, McGowan
SJ
, Zhu
Y
, Brooks
RW
, et al.. Identification of HSP90 inhibitors as a novel class of senolytics
. Nat Commun
. 2017
Sep
;8
(1
):422
.
[PubMed]
2041-172318.
Yanai
H
, Fraifeld
VE
. The role of cellular senescence in aging through the prism of Koch-like criteria
. Ageing Res Rev
. 2018
Jan
;41
:18
–33
.
[PubMed]
1568-163719.
Justice
JN
, Nambiar
AM
, Tchkonia
T
, LeBrasseur
NK
, Pascual
R
, Hashmi
SK
, et al.. Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study
. EBioMedicine
. 2019
Feb
;40
:554
–63
.
[PubMed]
2352-396420.
Yousefzadeh
MJ
, Zhu
Y
, McGowan
SJ
, Angelini
L
, Fuhrmann-Stroissnigg
H
, Xu
M
, et al.. Fisetin is a senotherapeutic that extends health and lifespan
. EBioMedicine
. 2018
Oct
;36
:18
–28
.
[PubMed]
2352-396421.
Schubert
D
, Currais
A
, Goldberg
J
, Finley
K
, Petrascheck
M
, Maher
P
. Geroneuroprotectors: Effective Geroprotectors for the Brain
. Trends Pharmacol Sci
. 2018
Dec
;39
(12
):1004
–7
.
[PubMed]
0165-614722.
Krasieva
TB
, Ehren
J
, O’Sullivan
T
, Tromberg
BJ
, Maher
P
. Cell and brain tissue imaging of the flavonoid fisetin using label-free two-photon microscopy
. Neurochem Int
. 2015
Oct
;89
:243
–8
.
[PubMed]
0197-018623.
Zhang
X
, Yin
J
, Liang
C
, Sun
Y
, Zhang
L
. UHPLC-Q-TOF-MS/MS Method Based on Four-Step Strategy for Metabolism Study of Fisetin in Vitro and in Vivo
. J Agric Food Chem
. 2017
Dec
;65
(50
):10959
–72
.
[PubMed]
0021-856125.
Kaeberlein
M
. How healthy is the healthspan concept
. Geroscience
. 2018
Aug
;40
(4
):361
–4
.
[PubMed]
2509-271526.
Graham
GG
, Punt
J
, Arora
M
, Day
RO
, Doogue
MP
, Duong
JK
, et al.. Clinical pharmacokinetics of metformin
. Clin Pharmacokinet
. 2011
Feb
;50
(2
):81
–98
.
[PubMed]
0312-596327.
Bailey
CJ
, Wilcock
C
, Scarpello
JH
. Metformin and the intestine
. Diabetologia
. 2008
Aug
;51
(8
):1552
–3
.
[PubMed]
0012-186X28.
Paleari
L
, Burhenne
J
, Weiss
J
, Foersch
S
, Roth
W
, Parodi
A
, et al.. High Accumulation of Metformin in Colonic Tissue of Subjects With Diabetes or the Metabolic Syndrome
. Gastroenterology
. 2018
Apr
;154
(5
):1543
–5
.
[PubMed]
0016-508529.
Wu
T
, Horowitz
M
, Rayner
CK
. New insights into the anti-diabetic actions of metformin: from the liver to the gut
. Expert Rev Gastroenterol Hepatol
. 2017
Feb
;11
(2
):157
–66
.
[PubMed]
1747-412430.
Buse
JB
, DeFronzo
RA
, Rosenstock
J
, Kim
T
, Burns
C
, Skare
S
, et al.. The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies
. Diabetes Care
. 2016
Feb
;39
(2
):198
–205
.
[PubMed]
1935-554831.
Bahne
E
, Sun
EW
, Young
RL
, Hansen
M
, Sonne
DP
, Hansen
JS
, et al.. Metformin-induced glucagon-like peptide-1 secretion contributes to the actions of metformin in type 2 diabetes
. JCI Insight
. 2018
Dec
;3
(23
):93936
.
[PubMed]
2379-370832.
Pakos-Zebrucka
K
, Koryga
I
, Mnich
K
, Ljujic
M
, Samali
A
, Gorman
AM
. The integrated stress response
. EMBO Rep
. 2016
Oct
;17
(10
):1374
–95
.
[PubMed]
1469-221X33.
Coll
AP
, Chen
M
, Taskar
P
, Rimington
D
, Patel
S
, Tadross
J
, et al.. GDF15 and the beneficial actions of metformin in pre-diabetes
. bioRxiv
. 34.
Musi
N
, Hirshman
MF
, Nygren
J
, Svanfeldt
M
, Bavenholm
P
, Rooyackers
O
, et al.. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes
. Diabetes
. 2002
Jul
;51
(7
):2074
–81
.
[PubMed]
0012-179735.
Boyle
JG
, Logan
PJ
, Jones
GC
, Small
M
, Sattar
N
, Connell
JM
, et al.. AMP-activated protein kinase is activated in adipose tissue of individuals with type 2 diabetes treated with metformin: a randomised glycaemia-controlled crossover study
. Diabetologia
. 2011
Jul
;54
(7
):1799
–809
.
[PubMed]
0012-186X36.
Sun
EW
, Martin
AM
, Wattchow
DA
, de Fontgalland
D
, Rabbitt
P
, Hollington
P
, et al.. Metformin Triggers PYY Secretion in Human Gut Mucosa
. J Clin Endocrinol Metab
. 2019
Jul
;104
(7
):2668
–74
.
[PubMed]
0021-972X37.
Vara-Ciruelos
D
, Russell
FM
, Hardie
DG
. The strange case of AMPK and cancer: Dr Jekyll or Mr Hyde? †
. Open Biol
. 2019
Jul
;9
(7
):190099
.
[PubMed]
2046-244138.
Lin
SC
, Hardie
DG
. AMPK: Sensing Glucose as well as Cellular Energy Status
. Cell Metab
. 2018
Feb
;27
(2
):299
–313
.
[PubMed]
1550-413139.
Bridges
HR
, Sirviö
VA
, Agip
AN
, Hirst
J
. Molecular features of biguanides required for targeting of mitochondrial respiratory complex I and activation of AMP-kinase
. BMC Biol
. 2016
Aug
;14
(1
):65
.
[PubMed]
1741-700740.
Glossmann
HH
, Lutz
OM
. Commentary: Lactate-Induced Glucose Output Is Unchanged by Metformin at a Therapeutic Concentration-A Mass Spectrometry Imaging Study of the Perfused Rat Liver
. Front Pharmacol
. 2019
Feb
;10
:90
.
[PubMed]
1663-981241.
Cameron
AR
, Logie
L
, Patel
K
, Erhardt
S
, Bacon
S
, Middleton
P
, et al.. Metformin selectively targets redox control of complex I energy transduction
. Redox Biol
. 2018
Apr
;14
:187
–97
.
[PubMed]
2213-231742.
Robb
EL
, Hall
AR
, Prime
TA
, Eaton
S
, Szibor
M
, Viscomi
C
, et al.. Control of mitochondrial superoxide production by reverse electron transport at complex I
. J Biol Chem
. 2018
Jun
;293
(25
):9869
–79
.
[PubMed]
0021-925843.
Zhang
CS
, Li
M
, Ma
T
, Zong
Y
, Cui
J
, Feng
JW
, et al.. Metformin Activates AMPK through the Lysosomal Pathway
. Cell Metab
. 2016
Oct
;24
(4
):521
–2
.
[PubMed]
1550-413144.
Check Hayden
E
. Anti-ageing pill pushed as bona fide drug
. Nature
. 2015
Jun
;522
(7556
):265
–6
.
[PubMed]
0028-083645.
Bulterijs
S
, Hull
RS
, Björk
VC
, Roy
AG
. It is time to classify biological aging as a disease
. Front Genet
. 2015
Jun
;6
:205
.
[PubMed]
1664-802146.
Armato
JP
, DeFronzo
RA
, Abdul-Ghani
M
, Ruby
RJ
. Successful treatment of prediabetes in clinical practice using physiological assessment (STOP DIABETES)
. Lancet Diabetes Endocrinol
. 2018
Oct
;6
(10
):781
–9
.
[PubMed]
2213-858747.
Salpeter
SR
, Buckley
NS
, Kahn
JA
, Salpeter
EE
. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus
. Am J Med
. 2008
Feb
;121
(2
):149
–157.e2
.
[PubMed]
0002-934348.
Glossmann
H
, Reider
N
. A marriage of two “Methusalem” drugs for the treatment of psoriasis?: arguments for a pilot trial with metformin as add-on for methotrexate
. Dermatoendocrinol
. 2013
Apr
;5
(2
):252
–63
.
[PubMed]
1938-197249.
50.
Cha
Y
, Erez
T
, Reynolds
IJ
, Kumar
D
, Ross
J
, Koytiger
G
, et al.. Drug repurposing from the perspective of pharmaceutical companies
. Br J Pharmacol
. 2018
Jan
;175
(2
):168
–80
.
[PubMed]
0007-118851.
Espeland
MA
, Crimmins
EM
, Grossardt
BR
, Crandall
JP
, Gelfond
JA
, Harris
TB
, et al.; Multimorbidity Clinical Trials Consortium
. Clinical Trials Targeting Aging and Age-Related Multimorbidity
. J Gerontol A Biol Sci Med Sci
. 2017
Mar
;72
(3
):355
–61
.
[PubMed]
1758-535X52.
Barzilai
N
, Cuervo
AM
, Austad
S
. Aging as a Biological Target for Prevention and Therapy
. JAMA
. 2018
Oct
;320
(13
):1321
–2
.
[PubMed]
0098-748453.
Mullard
A
. Anti-ageing pipeline starts to mature
. Nat Rev Drug Discov
. 2018
Sep
;17
(9
):609
–12
.
[PubMed]
1474-177654.
Espinoza
SE
, Musi
N
, Wang
CP
, Michalek
J
, Orsak
B
, Romo
T
, et al.. Rationale and Study Design of a Randomized Clinical Trial of Metformin to Prevent Frailty in Older Adults with Pre-Diabetes
. J Gerontol A Biol Sci Med Sci
. 2019
Mar
;glz078
.
[PubMed]
1758-535X55.
Konopka
AR
, Miller
BF
. Taming expectations of metformin as a treatment to extend healthspan
. Geroscience
. 2019
Apr
;41
(2
):101
–8
.
[PubMed]
2509-271556.
Griffin
SJ
, Bethel
MA
, Holman
RR
, Khunti
K
, Wareham
N
, Brierley
G
, et al.. Metformin in non-diabetic hyperglycaemia: the GLINT feasibility RCT
. Health Technol Assess
. 2018
Apr
;22
(18
):1
–64
.
[PubMed]
1366-527857.
Justice
JN
, Ferrucci
L
, Newman
AB
, Aroda
VR
, Bahnson
JL
, Divers
J
, et al.. A framework for selection of blood-based biomarkers for geroscience-guided clinical trials: report from the TAME Biomarkers Workgroup
. Geroscience
. 2018
Dec
;40
(5-6
):419
–36
.
[PubMed]
2509-271558.
Kulkarni
AS
, Brutsaert
EF
, Anghel
V
, Zhang
K
, Bloomgarden
N
, Pollak
M
, et al.. Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults
. Aging Cell
. 2018
Apr
;17
(2
):e12723
.
[PubMed]
1474-971859.
Leidal
AM
, Levine
B
, Debnath
J
. Autophagy and the cell biology of age-related disease
. Nat Cell Biol
. 2018
Dec
;20
(12
):1338
–48
.
[PubMed]
1465-739260.
Ren
J
, Zhang
Y
. Targeting Autophagy in Aging and Aging-Related Cardiovascular Diseases
. Trends Pharmacol Sci
. 2018
Dec
;39
(12
):1064
–76
.
[PubMed]
0165-614761.
Kanamori
H
, Naruse
G
, Yoshida
A
, Minatoguchi
S
, Watanabe
T
, Kawaguchi
T
, et al.. Metformin Enhances Autophagy and Provides Cardioprotection in δ-Sarcoglycan Deficiency-Induced Dilated Cardiomyopathy
. Circ Heart Fail
. 2019
Apr
;12
(4
):e005418
.
[PubMed]
1941-328962.
Diaz-Morales
N
, Iannantuoni
F
, Escribano-Lopez
I
, Bañuls
C
, Rovira-Llopis
S
, Sola
E
, et al.. Does Metformin Modulate Endoplasmic Reticulum Stress and Autophagy in Type 2 Diabetic Peripheral Blood Mononuclear Cells
. Antioxid Redox Signal
. 2018
Jun
;28
(17
):1562
–9
.
[PubMed]
1523-086464.
Yerevanian
A
, Soukas
AA
. Metformin: Mechanisms in Human Obesity and Weight Loss
. Curr Obes Rep
. 2019
Jun
;8
(2
):156
–64
.
[PubMed]
2162-496865.
Tseng
CH
. Metformin and risk of hepatocellular carcinoma in patients with type 2 diabetes
. Liver Int
. 2018
Nov
;38
(11
):2018
–27
.
[PubMed]
1478-322366.
Stevens
RJ
, Ali
R
, Bankhead
CR
, Bethel
MA
, Cairns
BJ
, Camisasca
RP
, et al.. Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials
. Diabetologia
. 2012
Oct
;55
(10
):2593
–603
.
[PubMed]
0012-186X67.
Noto
H
, Goto
A
, Tsujimoto
T
, Noda
M
. Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis
. PLoS One
. 2012
;7
(3
):e33411
.
[PubMed]
1932-620368.
Boussageon
R
, Supper
I
, Bejan-Angoulvant
T
, Kellou
N
, Cucherat
M
, Boissel
JP
, et al.. Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials
. PLoS Med
. 2012
;9
(4
):e1001204
.
[PubMed]
1549-127769.
Griffin
SJ
, Leaver
JK
, Irving
GJ
. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes
. Diabetologia
. 2017
Sep
;60
(9
):1620
–9
.
[PubMed]
0012-186X70.
Wang
CP
, Lorenzo
C
, Habib
SL
, Jo
B
, Espinoza
SE
. Differential effects of metformin on age related comorbidities in older men with type 2 diabetes
. J Diabetes Complications
. 2017
Apr
;31
(4
):679
–86
.
[PubMed]
1056-872771.
Campbell
JM
, Bellman
SM
, Stephenson
MD
, Lisy
K
. Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis
. Ageing Res Rev
. 2017
Nov
;40
:31
–44
.
[PubMed]
1568-163772.
Bannister
CA
, Holden
SE
, Jenkins-Jones
S
, Morgan
CL
, Halcox
JP
, Schernthaner
G
, et al.. Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls
. Diabetes Obes Metab
. 2014
Nov
;16
(11
):1165
–73
.
[PubMed]
1462-890273.
Xu
H
, Aldrich
MC
, Chen
Q
, Liu
H
, Peterson
NB
, Dai
Q
, et al.. Validating drug repurposing signals using electronic health records: a case study of metformin associated with reduced cancer mortality
. J Am Med Inform Assoc
. 2015
Jan
;22
(1
):179
–91
.
[PubMed]
1527-974X74.
Nathan
DM
, Knowler
WC
, Edelstein
S
, Crandall
JP
, Dabelea
D
, Goldberg
RB
, et al.; Diabetes Prevention Program Research Group
. Long-term Effects of Metformin on Diabetes Prevention: Identification of Subgroups That Benefited Most in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study
. Diabetes Care
. 2019
Apr
;42
(4
):601
–8
.
[PubMed]
0149-599276.
Bonaccio
M
, Di Castelnuovo
A
, Costanzo
S
, Gialluisi
A
, Persichillo
M
, Cerletti
C
, et al.. Mediterranean diet and mortality in the elderly: a prospective cohort study and a meta-analysis
. Br J Nutr
. 2018
Oct
;120
(8
):841
–54
.
[PubMed]
0007-114577.
Estruch
R
, Ros
E
, Salas-Salvadó
J
, Covas
MI
, Corella
D
, Arós
F
, et al.; PREDIMED Study Investigators
. Primary prevention of cardiovascular disease with a Mediterranean diet
. N Engl J Med
. 2013
Apr
;368
(14
):1279
–90
.
[PubMed]
0028-479378.
Agarwal
A
, Ioannidis
JP
. PREDIMED trial of Mediterranean diet: retracted, republished, still trusted
. BMJ
. 2019
Feb
;364
:l341
.
[PubMed]
0959-813879.
Barzilai
N
, Crandall
JP
, Kritchevsky
SB
, Espeland
MA
. Metformin as a Tool to Target Aging
. Cell Metab
. 2016
Jun
;23
(6
):1060
–5
.
[PubMed]
1550-413180.
Mack
HID
, Heimbucher
T
, Murphy
CT
: The nematode Caenorhabditis elegans as a model for aging research.
Drug Discov Today Dis Model. DOI: 81.
Onken
B
, Driscoll
M
. Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN-1
. PLoS One
. 2010
Jan
;5
(1
):e8758
.
[PubMed]
1932-620382.
Madeo
F
, Carmona-Gutierrez
D
, Hofer
SJ
, Kroemer
G
. Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential
. Cell Metab
. 2019
Mar
;29
(3
):592
–610
.
[PubMed]
1550-413183.
Bansal
A
, Zhu
LJ
, Yen
K
, Tissenbaum
HA
. Uncoupling lifespan and healthspan in Caenorhabditis elegans longevity mutants
. Proc Natl Acad Sci USA
. 2015
Jan
;112
(3
):E277
–86
.
[PubMed]
0027-842484.
De Magalhaes Filho
CD
, Henriquez
B
, Seah
NE
, Evans
RM
, Lapierre
LR
, Dillin
A
. Visible light reduces C. elegans longevity
. Nat Commun
. 2018
Mar
;9
(1
):927
.
[PubMed]
2041-172385.
Cabreiro
F
, Au
C
, Leung
KY
, Vergara-Irigaray
N
, Cochemé
HM
, Noori
T
, et al.. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism
. Cell
. 2013
Mar
;153
(1
):228
–39
.
[PubMed]
0092-867486.
De Haes
W
, Frooninckx
L
, Van Assche
R
, Smolders
A
, Depuydt
G
, Billen
J
, et al.. Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2
. Proc Natl Acad Sci USA
. 2014
Jun
;111
(24
):E2501
–9
.
[PubMed]
0027-842487.
88.
Kim
J
, Lee
HY
, Ahn
J
, Hyun
M
, Lee
I
, Min
KJ
, et al.. NHX-5, an Endosomal Na+/H+ Exchanger, Is Associated with Metformin Action
. J Biol Chem
. 2016
Aug
;291
(35
):18591
–9
.
[PubMed]
0021-925889.
Chen
J
, Ou
Y
, Li
Y
, Hu
S
, Shao
LW
, Liu
Y
. Metformin extends C. elegans lifespan through lysosomal pathway
. eLife
. 2017
Oct
;6
:e31268
.
[PubMed]
2050-084X90.
Piper
MD
, Partridge
L
. Drosophila as a model for ageing
. Biochim Biophys Acta Mol Basis Dis
. 2018
Sep
;1864
(9
9 Pt A
):2707
–17
.
[PubMed]
0925-443991.
Slack
C
, Foley
A
, Partridge
L
. Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila
. PLoS One
. 2012
;7
(10
):e47699
.
[PubMed]
1932-620392.
Prasad
H
, Rao
R
. Histone deacetylase-mediated regulation of endolysosomal pH
. J Biol Chem
. 2018
May
;293
(18
):6721
–35
.
[PubMed]
0021-925893.
Kim
J
, You
YJ
. Regulation of organelle function by metformin
. IUBMB Life
. 2017
Jul
;69
(7
):459
–69
.
[PubMed]
1521-654394.
Martin-Montalvo
A
, Mercken
EM
, Mitchell
SJ
, Palacios
HH
, Mote
PL
, Scheibye-Knudsen
M
, et al.. Metformin improves healthspan and lifespan in mice
. Nat Commun
. 2013
;4
(1
):2192
.
[PubMed]
2041-172395.
Strong
R
, Miller
RA
, Antebi
A
, Astle
CM
, Bogue
M
, Denzel
MS
, et al.. Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer
. Aging Cell
. 2016
Oct
;15
(5
):872
–84
.
[PubMed]
1474-971896.
Beck
JA
, Lloyd
S
, Hafezparast
M
, Lennon-Pierce
M
, Eppig
JT
, Festing
MF
, et al.. Genealogies of mouse inbred strains
. Nat Genet
. 2000
Jan
;24
(1
):23
–5
.
[PubMed]
1061-403697.
Bartke
A
. Growth Hormone and Aging: updated Review
. World J Mens Health
. 2019
Jan
;37
(1
):19
–30
.
[PubMed]
2287-420898.
Porter
KM
, Ward
M
, Hughes
CF
, O’Kane
M
, Hoey
L
, McCann
A
, et al.. Hyperglycemia and metformin use are associated with B-vitamin deficiency and cognitive dysfunction in older adults
. J Clin Endocrinol Metab
. 2019
Mar
;jc.2018-01791
.
[PubMed]
0021-972X99.
Braun
B
, Eze
P
, Stephens
BR
, Hagobian
TA
, Sharoff
CG
, Chipkin
SR
, et al.. Impact of metformin on peak aerobic capacity
. Appl Physiol Nutr Metab
. 2008
Feb
;33
(1
):61
–7
.
[PubMed]
1715-5312100.
Long
DE
, Peck
BD
, Martz
JL
, Tuggle
SC
, Bush
HM
, McGwin
G
, et al.. Metformin to Augment Strength Training Effective Response in Seniors (MASTERS): study protocol for a randomized controlled trial
. Trials
. 2017
Apr
;18
(1
):192
.
[PubMed]
1745-6215101.
Ruby
JG
, Smith
M
, Buffenstein
R
. Naked Mole-Rat mortality rates defy gompertzian laws by not increasing with age
. eLife
. 2018
Jan
;7
:e31157
.
[PubMed]
2050-084X© 2019 S. Karger AG, Basel
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