PMID- 12039436
OWN - NLM
STAT- MEDLINE
DCOM- 20020628
LR  - 20191106
IS  - 1568-1637 (Print)
IS  - 1568-1637 (Linking)
VI  - 1
IP  - 2
DP  - 2002 Apr
TI  - How does the brain control lifespan?
PG  - 155-65
AB  - There is generally a positive correlation between brain/body size ratio and 
      lifespan, particularly among mammals, suggesting a role for the brain in 
      determining lifespan. Recent studies in diverse organisms including nematodes, 
      flies and rodents have provided evidence that, indeed the brain may control 
      lifespan. Signaling pathways involved in both central nervous system and 
      peripheral stress responses and regulation of energy metabolism may play 
      important roles in lifespan determination. Indeed, genetic and environmental 
      manipulations of these systems can greatly affect lifespan by changing levels of 
      hormones that modulate energy metabolism, stress resistance and regenerative 
      capacity of cells throughout the body. A signal transduction pathway in neurons 
      involving receptors coupled to phosphatidylinositol-3-kinase, Akt and glycogen 
      synthase kinase-3beta appears to play a key role in regulation of longevity by 
      the brain. Mutations in genes that encode proteins in the insulin signaling 
      pathway can increase lifespan in C. elegans and Drosophila, this signaling 
      pathway in neurons in the brain may be particularly important in limiting 
      lifespan. Dietary restriction results in the upregulation of brain-derived 
      neurotrophic factor (BDNF) in the brain, which may increase the resistance of 
      neurons to aging. Interestingly, BDNF signaling in the brain can increase 
      peripheral insulin sensitivity, suggesting a mechanism whereby the brain can 
      control lifespan. We speculate that during evolution the brain took on the task 
      of monitoring and controlling peripheral energy metabolism, and thereby 
      regulating lifespan in the context of food availability. Roles for other 
      evolutionarily conserved brain signaling pathways in lifespan determination are 
      likely to be discovered in the near future.
FAU - Mattson, Mark P
AU  - Mattson MP
AD  - Laboratory of Neurosciences-4F02, National Institute on Aging Gerontology 
      Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. 
      mattsonm@grc.nia.nih.gov
FAU - Duan, Wenzhen
AU  - Duan W
FAU - Maswood, Navin
AU  - Maswood N
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - England
TA  - Ageing Res Rev
JT  - Ageing research reviews
JID - 101128963
SB  - IM
MH  - Aging/*physiology
MH  - Animals
MH  - Brain/*physiology
MH  - Humans
MH  - Longevity/*physiology
RF  - 74
EDAT- 2002/06/01 10:00
MHDA- 2002/06/29 10:01
CRDT- 2002/06/01 10:00
PHST- 2002/06/01 10:00 [pubmed]
PHST- 2002/06/29 10:01 [medline]
PHST- 2002/06/01 10:00 [entrez]
AID - S1568163701000034 [pii]
AID - 10.1016/s1568-1637(01)00003-4 [doi]
PST - ppublish
SO  - Ageing Res Rev. 2002 Apr;1(2):155-65. doi: 10.1016/s1568-1637(01)00003-4.