PMID- 37790446
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
DP  - 2023 Sep 20
TI  - Caloric restriction promotes beta cell longevity and delays aging and senescence 
      by enhancing cell identity and homeostasis mechanisms.
LID - rs.3.rs-3311459 [pii]
LID - 10.21203/rs.3.rs-3311459/v1 [doi]
AB  - Caloric restriction (CR) extends organismal lifespan and health span by improving 
      glucose homeostasis mechanisms. How CR affects organellar structure and function 
      of pancreatic beta cells over the lifetime of the animal remains unknown. Here, 
      we used single nucleus transcriptomics to show that CR increases the expression 
      of genes for beta cell identity, protein processing, and organelle homeostasis. 
      Gene regulatory network analysis link this transcriptional phenotype to 
      transcription factors involved in beta cell identity (Mafa) and homeostasis 
      (Atf6). Imaging metabolomics further demonstrates that CR beta cells are more 
      energetically competent. In fact, high-resolution light and electron microscopy 
      indicates that CR reduces beta cell mitophagy and increases mitochondria mass, 
      increasing mitochondrial ATP generation. Finally, we show that long-term CR 
      delays the onset of beta cell aging and senescence to promote longevity by 
      reducing beta cell turnover. Therefore, CR could be a feasible approach to 
      preserve compromised beta cells during aging and diabetes.
FAU - Dos Santos, Cristiane
AU  - Dos Santos C
AD  - Vanderbilt University, Department of Molecular Physiology and Biophysics, 
      Nashville, TN USA.
FAU - Shrestha, Shristi
AU  - Shrestha S
AD  - Vanderbilt University, Department of Molecular Physiology and Biophysics, 
      Nashville, TN USA.
FAU - Cottam, Matthew
AU  - Cottam M
AUID- ORCID: 0000-0003-0619-1605
AD  - Vanderbilt University, Department of Molecular Physiology and Biophysics, 
      Nashville, TN USA.
FAU - Perkins, Guy
AU  - Perkins G
AD  - National Center for Imaging and Microscopy Research, University of California San 
      Diego, La Jolla, CA USA.
FAU - Lev-Ram, Varda
AU  - Lev-Ram V
AD  - University of California San Diego, Department of Pharmacology, School of 
      Medicine. La Jolla, CA USA.
FAU - Roy, Birbickram
AU  - Roy B
AD  - Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, 
      Edmonton, Canada.
FAU - Acree, Christopher
AU  - Acree C
AD  - Vanderbilt University, Department of Molecular Physiology and Biophysics, 
      Nashville, TN USA.
FAU - Kim, Keun-Young
AU  - Kim KY
AD  - National Center for Imaging and Microscopy Research, University of California San 
      Diego, La Jolla, CA USA.
FAU - Deerinck, Thomas
AU  - Deerinck T
AD  - National Center for Imaging and Microscopy Research, University of California San 
      Diego, La Jolla, CA USA.
FAU - Cutler, Melanie
AU  - Cutler M
AD  - Vanderbilt University, Department of Molecular Physiology and Biophysics, 
      Nashville, TN USA.
FAU - Dean, Danielle
AU  - Dean D
AD  - Vanderbilt University, Department of Molecular Physiology and Biophysics, 
      Nashville, TN USA.
FAU - Cartailler, Jean Philippe
AU  - Cartailler JP
AUID- ORCID: 0000-0002-0312-2391
AD  - Vanderbilt University, Department of Molecular Physiology and Biophysics, 
      Nashville, TN USA.
FAU - MacDonald, Patrick E
AU  - MacDonald PE
AD  - Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, 
      Edmonton, Canada.
FAU - Hetzer, Martin
AU  - Hetzer M
AUID- ORCID: 0000-0002-2111-992X
AD  - Institute of Science and Technology Austria (ISTA), Vienna, Austria.
FAU - Ellisman, Mark
AU  - Ellisman M
AUID- ORCID: 0000-0001-8893-8455
AD  - National Center for Imaging and Microscopy Research, University of California San 
      Diego, La Jolla, CA USA.
FAU - Drigo, Rafael Arrojo E
AU  - Drigo RAE
AUID- ORCID: 0000-0001-7712-013X
AD  - Vanderbilt University, Department of Molecular Physiology and Biophysics, 
      Nashville, TN USA.
LA  - eng
GR  - R01 DK132669/DK/NIDDK NIH HHS/United States
GR  - U24 DK097771/DK/NIDDK NIH HHS/United States
GR  - U24 NS120055/NS/NINDS NIH HHS/United States
GR  - R24 GM137200/GM/NIGMS NIH HHS/United States
GR  - S10 OD021784/OD/NIH HHS/United States
GR  - R03 DK127484/DK/NIDDK NIH HHS/United States
GR  - R01 DA038896/DA/NIDA NIH HHS/United States
PT  - Preprint
DEP - 20230920
PL  - United States
TA  - Res Sq
JT  - Research square
JID - 101768035
PMC - PMC10543285
COIS- Declaration of Interest. The authors declare no competing interests.
EDAT- 2023/10/04 06:44
MHDA- 2023/10/04 06:45
PMCR- 2023/10/02
CRDT- 2023/10/04 04:04
PHST- 2023/10/04 06:44 [pubmed]
PHST- 2023/10/04 06:45 [medline]
PHST- 2023/10/04 04:04 [entrez]
PHST- 2023/10/02 00:00 [pmc-release]
AID - rs.3.rs-3311459 [pii]
AID - 10.21203/rs.3.rs-3311459/v1 [doi]
PST - epublish
SO  - Res Sq [Preprint]. 2023 Sep 20:rs.3.rs-3311459. doi: 10.21203/rs.3.rs-3311459/v1.