X-Message-Number: 30006
Date: Thu, 8 Nov 2007 21:46:54 -0800 (PST)
From: 
Subject: nighttime NSAIDs may accelerate aging

[Body temperature reduction, and melatonin supplementation have increased
lifespan in mammals. Nighttime (but not daytime) NSAIDs increase body
temperature, and suppress melatonin. This may explain why some (but not all)
humans studies with NSAIDS find increased mortality.]

Physiol Behav. 1996 Jan;59(1):133-9.
Nonsteroidal anti-inflammatory drugs alter body temperature and suppress
melatonin in humans.
    Murphy PJ, Myers BL, Badia P.
    Bowling Green State University, OH 43403, USA.
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin
synthesis in humans. Prostaglandins are involved in thermoregulation,
melatonin synthesis, and sleep. To determine effects of NSAIDs on body
temperature (BT) and melatonin synthesis (MT) in humans, and to elucidate
mechanisms by which NSAIDs may alter sleep patterns, a series of experiments
using the NSAIDs aspirin and ibuprofen was conducted. Seventy-five subjects
were tested under several experimental protocols. BT after NSAID or placebo
was assessed in both between- and within-subjects designs at night and
during the day. MT levels were assessed after NSAID or placebo at night in a
within-subjects design. The normal nocturnal BT decrease was attenuated and
MT was suppressed after NSAID relative to after placebo administration.
Lower MT levels were associated with a relative flattening of BT. Daytime BT
was not affected by NSAIDs. These results are compatible with the hypothesis
that some of the behavioral changes associated with NSAIDs, including
changes in sleep, are due to changes in BT and MT. We speculate that NSAID
effects on sleep and BT are related to prostaglandin synthesis inhibition
and/or suppression of MT.
PMID: 8848472

[The most potent modulator of aging rate in cold blooded animals is
temperature. This may well also be the case in mammals as well.]

Science. 2006 Nov 3;314(5800):825-8.
Comment in:
Science. 2006 Nov 3;314(5800):773-4.
Transgenic mice with a reduced core body temperature have an increased life
span.
    Conti B, Sanchez-Alavez M, Winsky-Sommerer R, Morale MC, Lucero J,
Brownell S, Fabre V, Huitron-Resendiz S, Henriksen S, Zorrilla EP, de Lecea
L, Bartfai T. Harold L. Dorris Neurological Research Center, Scripps
Research Institute, La Jolla, CA 92037, USA.
    Reduction of core body temperature has been proposed to contribute to
the increased life span and the antiaging effects conferred by calorie
restriction (CR). Validation of this hypothesis has been difficult in
homeotherms, primarily due to a lack of experimental models. We report that
transgenic mice engineered to overexpress the uncoupling protein 2 in
hypocretin neurons (Hcrt-UCP2) have elevated hypothalamic temperature. The
effects of local temperature elevation on the central thermostat resulted in
a 0.3 degrees to 0.5 degrees C reduction of the core body temperature. Fed
ad libitum, Hcrt-UCP2 transgenic mice had the same caloric intake as their
wild-type littermates but had increased energy efficiency and a greater
median life span (12% increase in males; 20% increase in females). Thus,
modest, sustained reduction of core body temperature prolonged life span
independent of altered diet or CR.
PMID: 17082459

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