PMID- 32566245
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210703
IS  - 2056-3973 (Print)
IS  - 2056-3973 (Electronic)
IS  - 2056-3973 (Linking)
VI  - 6
DP  - 2020
TI  - Lifespan and healthspan benefits of exogenous H(2)S in C. elegans are independent 
      from effects downstream of eat-2 mutation.
PG  - 6
LID - 10.1038/s41514-020-0044-8 [doi]
LID - 6
AB  - Caloric restriction (CR) is one of the most effective interventions to prolong 
      lifespan and promote health. Recently, it has been suggested that hydrogen 
      sulfide (H(2)S) may play a pivotal role in mediating some of these CR-associated 
      benefits. While toxic at high concentrations, H(2)S at lower concentrations can 
      be biologically advantageous. H(2)S levels can be artificially elevated via 
      H(2)S-releasing donor drugs. In this study, we explored the function of a novel, 
      slow-releasing H(2)S donor drug (FW1256) and used it as a tool to investigate 
      H(2)S in the context of CR and as a potential CR mimetic. We show that exposure 
      to FW1256 extends lifespan and promotes health in Caenorhabditis elegans (C. 
      elegans) more robustly than some previous H(2)S-releasing compounds, including 
      GYY4137. We looked at the extent to which FW1256 reproduces CR-associated 
      physiological effects in normal-feeding C. elegans. We found that FW1256 promoted 
      healthy longevity to a similar degree as CR but with fewer fitness costs. In 
      contrast to CR, FW1256 actually enhanced overall reproductive capacity and did 
      not reduce adult body length. FW1256 further extended the lifespan of already 
      long-lived eat-2 mutants without further detriments in developmental timing or 
      fertility, but these lifespan and healthspan benefits required H(2)S exposure to 
      begin early in development. Taken together, these observations suggest that 
      FW1256 delivers exogenous H(2)S efficiently and supports a role for H(2)S in 
      mediating longevity benefits of CR. Delivery of H(2)S via FW1256, however, does 
      not mimic CR perfectly, suggesting that the role of H(2)S in CR-associated 
      longevity is likely more complex than previously described.
CI  - (c) The Author(s) 2020.
FAU - Ng, Li Theng
AU  - Ng LT
AD  - Ageing Research Laboratory, Science Division, Yale-NUS College, Singapore, 138527 
      Singapore. ISNI: 0000 0004 4651 0380. GRID: grid.463064.3
AD  - Department of Pharmacology, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore, 117600 Singapore. ISNI: 0000 0001 2180 6431. GRID: 
      grid.4280.e
AD  - Neurobiology Programme, Life Sciences Institute, National University of 
      Singapore, Singapore, 117456 Singapore. ISNI: 0000 0001 2180 6431. GRID: 
      grid.4280.e
FAU - Ng, Li Fang
AU  - Ng LF
AD  - Ageing Research Laboratory, Science Division, Yale-NUS College, Singapore, 138527 
      Singapore. ISNI: 0000 0004 4651 0380. GRID: grid.463064.3
FAU - Tang, Richard Ming Yi
AU  - Tang RMY
AD  - Department of Biochemistry, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore, 117596 Singapore. ISNI: 0000 0001 2180 6431. GRID: 
      grid.4280.e
AD  - Neurobiology Programme, Life Sciences Institute, National University of 
      Singapore, Singapore, 117456 Singapore. ISNI: 0000 0001 2180 6431. GRID: 
      grid.4280.e
AD  - NUS Graduate School for Integrative Sciences & Engineering, National University 
      of Singapore, Singapore, 117456 Singapore. ISNI: 0000 0001 2180 6431. GRID: 
      grid.4280.e
FAU - Barardo, Diogo
AU  - Barardo D
AD  - Ageing Research Laboratory, Science Division, Yale-NUS College, Singapore, 138527 
      Singapore. ISNI: 0000 0004 4651 0380. GRID: grid.463064.3
AD  - Department of Biochemistry, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore, 117596 Singapore. ISNI: 0000 0001 2180 6431. GRID: 
      grid.4280.e
FAU - Halliwell, Barry
AU  - Halliwell B
AD  - Department of Biochemistry, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore, 117596 Singapore. ISNI: 0000 0001 2180 6431. GRID: 
      grid.4280.e
AD  - Neurobiology Programme, Life Sciences Institute, National University of 
      Singapore, Singapore, 117456 Singapore. ISNI: 0000 0001 2180 6431. GRID: 
      grid.4280.e
FAU - Moore, Philip Keith
AU  - Moore PK
AD  - Department of Pharmacology, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore, 117600 Singapore. ISNI: 0000 0001 2180 6431. GRID: 
      grid.4280.e
AD  - Neurobiology Programme, Life Sciences Institute, National University of 
      Singapore, Singapore, 117456 Singapore. ISNI: 0000 0001 2180 6431. GRID: 
      grid.4280.e
FAU - Gruber, Jan
AU  - Gruber J
AD  - Ageing Research Laboratory, Science Division, Yale-NUS College, Singapore, 138527 
      Singapore. ISNI: 0000 0004 4651 0380. GRID: grid.463064.3
AD  - Department of Biochemistry, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore, 117596 Singapore. ISNI: 0000 0001 2180 6431. GRID: 
      grid.4280.e
LA  - eng
PT  - Journal Article
DEP - 20200610
PL  - England
TA  - NPJ Aging Mech Dis
JT  - NPJ aging and mechanisms of disease
JID - 101678947
PMC - PMC7287109
OTO - NOTNLM
OT  - Ageing
OT  - Drug discovery
COIS- Competing interestsThe authors declare no competing interests.
EDAT- 2020/06/23 06:00
MHDA- 2020/06/23 06:01
PMCR- 2020/06/10
CRDT- 2020/06/23 06:00
PHST- 2019/03/18 00:00 [received]
PHST- 2020/03/12 00:00 [accepted]
PHST- 2020/06/23 06:00 [entrez]
PHST- 2020/06/23 06:00 [pubmed]
PHST- 2020/06/23 06:01 [medline]
PHST- 2020/06/10 00:00 [pmc-release]
AID - 44 [pii]
AID - 10.1038/s41514-020-0044-8 [doi]
PST - epublish
SO  - NPJ Aging Mech Dis. 2020 Jun 10;6:6. doi: 10.1038/s41514-020-0044-8. eCollection 
      2020.