Perspectives on the membrane fatty acid unsaturation/pacemaker hypotheses of metabolism and aging.
The membrane pacemaker hypotheses of metabolism and aging are distinct, but interrelated hypotheses positing that increases in unsaturation of lipids within membranes are correlated with increasing basal metabolic rate and decreasing longevity, respectively. The two hypotheses each have evidence that either supports or contradicts them, but consensus has failed to emerge. In this review, we identify sources of weakness of previous studies supporting and contradicting these hypotheses and suggest different methods and lines of inquiry. The link between fatty acyl composition of membranes and membrane-bound protein activity is a central tenet of the membrane pacemaker hypothesis of metabolism, but the mechanism by which unsaturation would change protein activity is not well defined and, whereas fatty acid desaturases have been put forward by some as the mechanism behind evolutionary differences in fatty acyl composition of phospholipids among organisms, there have been no studies to differentiate whether desaturases have been more affected by natural selection on aging and metabolic rate than have elongases or acyltransferases. Past analyses have been hampered by potentially incorrect estimates of the peroxidizability of lipids and longevity of study animals, and by the confounding effect of phylogeny. According to some authors, body mass may also be a confounding effect that should be taken into account, though this is not universally accepted. Further research on this subject should focus more on mechanisms and take weaknesses of past studies into account.
Department of Evolution, Ecology and Organismal Biology, Ohio State University, Columbus, OH 43210-1293, USA. Electronic address: calhoon.18@osu.edu.
Elisabeth A
EA
Calhoon
Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI 48109, USA.
Jennifer
J
Ro
Department of Evolution, Ecology and Organismal Biology, Ohio State University, Columbus, OH 43210-1293, USA.
Joseph B
JB
Williams
D000818:Animals; D016922:Cellular Senescence; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D008136:Longevity; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D008563:Membrane Lipids; D010743:Phospholipids
Acyl composition; Longevity; Membrane pacemaker; Metabolic rate; Peroxidation; Phospholipids