Thermoregulation with age: role of beta-adrenergic signal transduction.
The predominance of the evidence from our studies indicates that beta 3-adrenergic-mediated thermogenesis in interscapular BAT is impaired with age. Moreover, upon exposure to cold, beta-adrenergic responsiveness in BAT is restored. However, the exact nature of the beta 3-adrenergic upregulation is unknown. When senescent rats are exposed to cold for as a little as 1 h, the increase in GDP binding is equal to the response in young rats. This indicates that any cold-induced upregulation of the beta-adrenergic signal transduction pathway must respond within this time frame. The senescent rats employed in our studies have been reared throughout their life at or near thermoneutrality. We hypothesize that under such conditions, beta 3-adrenergic signal transduction atrophies with age, whereas the induction pathways for the components of this signal transduction system remain intact. For example, the beta 3-adrenergic stimulation of UCP mRNA in BAT from senescent rats maintained at thermoneutrality is 54% of that of young rats. Upon exposure to the cold, possibly through a combination of enhanced beta 3AR-adenylyl cyclase coupling or enhanced gene expression of components in the signal transduction pathway or both, beta 3-adrenergic responsiveness is restored in the senescent rat.
Scarpace
P J
PJ
Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida 32608-1197, USA.
D002001:Adipose Tissue, Brown / Q000502:physiology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000375:Aging; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics; D003080:Cold Temperature; D015870:Gene Expression; D006153:Guanosine Diphosphate / Q000378:metabolism; D007473:Ion Channels; D007545:Isoproterenol / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D000071256:Uncoupling Protein 1
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D000071256:Uncoupling Protein 1; D006153:Guanosine Diphosphate; D007545:Isoproterenol; C033394:CGP 12177