PMID- 38064506
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20240320
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 120
IP  - 50
DP  - 2023 Dec 12
TI  - Late-life shift in caloric intake affects fly metabolism and longevity.
PG  - e2311019120
LID - 10.1073/pnas.2311019120 [doi]
LID - e2311019120
AB  - The prevalence of obesity is increasing in older adults and contributes to 
      age-related decline. Caloric restriction (CR) alleviates obesity phenotypes and 
      delays the onset of age-related changes. However, how late in life organisms 
      benefit from switching from a high-(H) to a low-calorie (L) diet is unclear. We 
      transferred male flies from a H to a L (HL) diet or vice versa (LH) at different 
      times during life. Both shifts immediately change fly rate of aging even when 
      applied late in life. HL shift rapidly reduces fly mortality rate to briefly 
      lower rate than in flies on a constant L diet, and extends lifespan. 
      Transcriptomic analysis uncovers that flies aged on H diet have acquired 
      increased stress response, which may have temporal advantage over flies aged on L 
      diet and leads to rapid decrease in mortality rate after HL switch. Conversely, a 
      LH shift increases mortality rate, which is temporarily higher than in flies aged 
      on a H diet, and shortens lifespan. Unexpectedly, more abundant transcriptomic 
      changes accompanied LH shift, including increase in ribosome biogenesis, stress 
      response and growth. These changes reflect protection from sudden release of ROS, 
      energy storage, and use of energy to growth, which all likely contribute to 
      higher mortality rate. As the beneficial effects of CR on physiology and lifespan 
      are conserved across many organisms, our study provides framework to study 
      underlying mechanisms of CR interventions that counteract the detrimental effects 
      of H diets and reduce rate of aging even when initiated later in life.
FAU - Li, Michael
AU  - Li M
AUID- ORCID: 0009-0000-1365-815X
AD  - Department of Genetics and Genome Sciences, University of Connecticut Health 
      Center, Farmington, CT 06030.
FAU - Macro, Jacob
AU  - Macro J
AD  - Department of Genetics and Genome Sciences, University of Connecticut Health 
      Center, Farmington, CT 06030.
FAU - Meadows, Kali
AU  - Meadows K
AD  - Department of Genetics and Genome Sciences, University of Connecticut Health 
      Center, Farmington, CT 06030.
FAU - Mishra, Dushyant
AU  - Mishra D
AD  - Department of Genetics and Genome Sciences, University of Connecticut Health 
      Center, Farmington, CT 06030.
FAU - Martin, Dominique
AU  - Martin D
AD  - Department of Genetics and Genome Sciences, University of Connecticut Health 
      Center, Farmington, CT 06030.
FAU - Olson, Sara
AU  - Olson S
AUID- ORCID: 0009-0009-1064-9974
AD  - Department of Genetics and Genome Sciences, University of Connecticut Health 
      Center, Farmington, CT 06030.
AD  - Institute for Systems Genomics, School of Medicine, University of Connecticut 
      Health Center, Farmington, CT 06030.
FAU - Huggins, Billy Joe
AU  - Huggins BJ
AD  - Department of Genetics and Genome Sciences, University of Connecticut Health 
      Center, Farmington, CT 06030.
FAU - Graveley, Brenton R
AU  - Graveley BR
AUID- ORCID: 0000-0001-5777-5892
AD  - Department of Genetics and Genome Sciences, University of Connecticut Health 
      Center, Farmington, CT 06030.
AD  - Institute for Systems Genomics, School of Medicine, University of Connecticut 
      Health Center, Farmington, CT 06030.
FAU - Li, James Y H
AU  - Li JYH
AD  - Department of Genetics and Genome Sciences, University of Connecticut Health 
      Center, Farmington, CT 06030.
AD  - Institute for Systems Genomics, School of Medicine, University of Connecticut 
      Health Center, Farmington, CT 06030.
FAU - Rogina, Blanka
AU  - Rogina B
AUID- ORCID: 0000-0003-1195-905X
AD  - Department of Genetics and Genome Sciences, University of Connecticut Health 
      Center, Farmington, CT 06030.
AD  - Institute for Systems Genomics, School of Medicine, University of Connecticut 
      Health Center, Farmington, CT 06030.
LA  - eng
GR  - T32 HG010463/HG/NHGRI NIH HHS/United States
GR  - R35 GM118140/GM/NIGMS NIH HHS/United States
GR  - R56 AG082788/AG/NIA NIH HHS/United States
GR  - U41 HG009889/HG/NHGRI NIH HHS/United States
GR  - R01 NS106844/NS/NINDS NIH HHS/United States
GR  - P30 AG067988/AG/NIA NIH HHS/United States
GR  - U24 HG009889/HG/NHGRI NIH HHS/United States
GR  - R01 NS120556/NS/NINDS NIH HHS/United States
GR  - R01 AG059586/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20231208
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
SB  - IM
EIN - Proc Natl Acad Sci U S A. 2024 Mar 12;121(11):e2402651121. PMID: 38437573
MH  - Animals
MH  - Male
MH  - *Longevity/physiology
MH  - *Energy Intake
MH  - Aging/physiology
MH  - Caloric Restriction
MH  - Drosophila melanogaster/physiology
MH  - Obesity
PMC - PMC10723134
OTO - NOTNLM
OT  - Drosophila melanogaster
OT  - aging
OT  - caloric restriction
OT  - lifespan
OT  - obesity
COIS- Competing interests statement:The authors declare no competing interest.
EDAT- 2023/12/08 18:42
MHDA- 2023/12/17 17:41
PMCR- 2024/06/08
CRDT- 2023/12/08 13:44
PHST- 2024/06/08 00:00 [pmc-release]
PHST- 2023/12/17 17:41 [medline]
PHST- 2023/12/08 18:42 [pubmed]
PHST- 2023/12/08 13:44 [entrez]
AID - 202311019 [pii]
AID - 10.1073/pnas.2311019120 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2023 Dec 12;120(50):e2311019120. doi: 
      10.1073/pnas.2311019120. Epub 2023 Dec 8.