PMID- 27473756
OWN - NLM
STAT- MEDLINE
DCOM- 20171016
LR  - 20171210
IS  - 1873-6815 (Electronic)
IS  - 0531-5565 (Linking)
VI  - 83
DP  - 2016 Oct
TI  - Caloric restriction and the precision-control of autophagy: A strategy for 
      delaying neurodegenerative disease progression.
PG  - 97-111
LID - S0531-5565(16)30217-0 [pii]
LID - 10.1016/j.exger.2016.07.014 [doi]
AB  - Caloric restriction (CR) is known to extend lifespan in most organisms, 
      indicating that nutrient and energy regulatory mechanisms impact aging. The 
      greatest risk factor for neurodegeneration is age; thus, the antiaging effects of 
      CR might attenuate progressive cell death and avert the aggregation of abnormal 
      proteins associated with neurodegenerative diseases. CR is a potent inducer of 
      autophagy, a tightly regulated intracellular process that facilitates recycling 
      of abnormal protein aggregates and damaged organelles into bioenergetic and 
      biosynthetic materials to maintain homeostasis. Thus, dysregulated autophagy can 
      lead to cellular dysfunction, abnormal protein accumulation, proteotoxicity and 
      subsequently the onset of several neurodegenerative diseases. Therefore, the 
      targeted and precision-controlled activation of autophagy represents a promising 
      therapeutic strategy. Non-pharmacological therapeutic interventions that delay 
      aging by modulating specific stages of autophagy might be beneficial against 
      premature aging, neurodegeneration and its associated ailments. However, the 
      dynamic and often compensatory cross-talk that exists between the protein 
      degradation pathways makes clinical translational approaches challenging. Here we 
      review the primary autophagy pathways in the context of age-related 
      neurodegenerative diseases, focusing on compensatory mechanisms and pathway 
      failure. By critically assessing each underlying molecular machinery, we reveal 
      their impact on aging and unmask the role of caloric restriction in changing 
      cellular fate by delayed aging through stimulation of autophagy. This may point 
      towards novel and better targeted interventions that exploit the autophagic 
      machinery in the treatment of neurodegenerative diseases.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Ntsapi, C
AU  - Ntsapi C
AD  - Department of Physiological Sciences, Faculty of Science, University of 
      Stellenbosch, Stellenbosch 7600, South Africa.
FAU - Loos, B
AU  - Loos B
AD  - Department of Physiological Sciences, Faculty of Science, University of 
      Stellenbosch, Stellenbosch 7600, South Africa. Electronic address: 
      bloos@sun.ac.za.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20160726
PL  - England
TA  - Exp Gerontol
JT  - Experimental gerontology
JID - 0047061
SB  - IM
MH  - Aging/*physiology
MH  - Animals
MH  - Autophagosomes/metabolism
MH  - Autophagy/*physiology
MH  - *Caloric Restriction
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Humans
MH  - Lysosomes/metabolism
MH  - Mice
MH  - Neurodegenerative Diseases/*diet therapy/metabolism
MH  - Rats
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Autophagic flux
OT  - Autophagolysosome
OT  - Autophagosome
OT  - Autophagy
OT  - Caloric restriction
OT  - Longevity
OT  - Lysosome
OT  - Neurodegeneration
EDAT- 2016/07/31 06:00
MHDA- 2017/10/17 06:00
CRDT- 2016/07/31 06:00
PHST- 2016/06/12 00:00 [received]
PHST- 2016/07/18 00:00 [revised]
PHST- 2016/07/25 00:00 [accepted]
PHST- 2016/07/31 06:00 [entrez]
PHST- 2016/07/31 06:00 [pubmed]
PHST- 2017/10/17 06:00 [medline]
AID - S0531-5565(16)30217-0 [pii]
AID - 10.1016/j.exger.2016.07.014 [doi]
PST - ppublish
SO  - Exp Gerontol. 2016 Oct;83:97-111. doi: 10.1016/j.exger.2016.07.014. Epub 2016 Jul 
      26.