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The timing of the shrew: continuous melatonin treatment maintains youthful rhythmic activity in aging Crocidura russula.

Magnanou E, Attia J, Fons R, Boeuf G, Falcon J - PLoS ONE (2009)

Bottom Line: Senescence is associated with a broad suite of physiological changes, including a decreased responsiveness of the circadian system.In both, a marked diel rhythm (low diurnal concentration; high nocturnal concentration) was present in young animals but then decreased in adults, and, as a result of a loss in the nocturnal production, was absent in old animals. 2) Daily locomotor activity rhythm was monitored in pre-senescent animals that had received either a subcutaneous melatonin implant, an empty implant or no implant at all.This is the first long term study (>500 days observation of the same individuals) that investigates the effects of continuous melatonin delivery.

View Article: PubMed Central - PubMed

Affiliation: UPMC University of Paris 06, UMR 7628, Banyuls/Mer, France. elodie.magnanou@obs-banyuls.fr

ABSTRACT

Background: Laboratory conditions ify the extrinsic factors that determine the wild expected lifespan and release the intrinsic or potential lifespan. Thus, wild animals reared in a laboratory often show an increased lifespan, and consequently an increased senescence phase. Senescence is associated with a broad suite of physiological changes, including a decreased responsiveness of the circadian system. The time-keeping hormone melatonin, an important chemical player in this system, is suspected to have an anti-aging role. The Greater White-toothed shrew Crocidura russula is an ideal study model to address questions related to aging and associated changes in biological functions: its lifespan is short and is substantially increased in captivity; daily and seasonal rhythms, while very marked the first year of life, are dramatically altered during the senescence process which starts during the second year. Here we report on an investigation of the effects of melatonin administration on locomotor activity of aging shrews.

Methodology/principal findings: 1) The diel fluctuations of melatonin levels in young, adult and aging shrews were quantified in the pineal gland and plasma. In both, a marked diel rhythm (low diurnal concentration; high nocturnal concentration) was present in young animals but then decreased in adults, and, as a result of a loss in the nocturnal production, was absent in old animals. 2) Daily locomotor activity rhythm was monitored in pre-senescent animals that had received either a subcutaneous melatonin implant, an empty implant or no implant at all. In non-implanted and sham-implanted shrews, the rhythm was well marked in adults. A marked degradation in both period and amplitude, however, started after the age of 14-16 months. This pattern was considerably delayed in melatonin-implanted shrews who maintained the daily rhythm for significantly longer.

Conclusions: This is the first long term study (>500 days observation of the same individuals) that investigates the effects of continuous melatonin delivery. As such, it sheds new light on the putative anti-aging role of melatonin by demonstrating that continuous melatonin administration delays the onset of senescence. In addition, the shrew appears to be a promising mammalian model for elucidating the precise relationships between melatonin and aging.

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Shrews' locomotor activity over the duration of the experiment.A: Actograms of a control and a melatonin-implanted shrew from the age of 12 to 30 months. Each line corresponds to one experimental day and there are 24 boxes per line (one box per hour). Nest exits are expressed as a grey scale: the darker the area, the higher the activity for a particular period. Blue arrows indicate each time a new implant was supplied. B: Daily activity profiles (mean±SEM) of controls (red) and melatonin-implanted (blue) shrews at, respectively, 12, 17, 21 and 30 months after the beginning of the experiment. Shrews were submitted to a natural light–dark regime. Grey boxes correspond to the night. Due to mortality, the number of individuals decreased during the experiment so that n was 11, 9, 6 and 4 at respectively month 12, 17, 21, and 30.
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pone-0005904-g003: Shrews' locomotor activity over the duration of the experiment.A: Actograms of a control and a melatonin-implanted shrew from the age of 12 to 30 months. Each line corresponds to one experimental day and there are 24 boxes per line (one box per hour). Nest exits are expressed as a grey scale: the darker the area, the higher the activity for a particular period. Blue arrows indicate each time a new implant was supplied. B: Daily activity profiles (mean±SEM) of controls (red) and melatonin-implanted (blue) shrews at, respectively, 12, 17, 21 and 30 months after the beginning of the experiment. Shrews were submitted to a natural light–dark regime. Grey boxes correspond to the night. Due to mortality, the number of individuals decreased during the experiment so that n was 11, 9, 6 and 4 at respectively month 12, 17, 21, and 30.

Mentions: All individuals, aged 11–15 mo, displayed a marked diel activity rhythm, which was the highest during the first half of the night (expressed as the number of nest exits per hour) (Fig. 3). A secondary smaller peak was observed early during the light phase (Fig. 3). This bimodal pattern had a marked 24 h periodicity of high amplitude. After month 15, the amplitude of the rhythm decreased dramatically in both controls and sham-implanted shrews, and was no longer observed after month 17 (Figs 3, 4). In parallel, the significance of the 24 h period also decreased to the point where it was no longer discernable (Figs 3, 4). In contrast, in the implanted animals (i) the first noticeable decrease in amplitude of the rhythm was delayed by 3 months and (ii) the 24 h period remained highly significant until death (Figs 3, 4). In addition, the second and, to a lesser extent, the third implants induced a temporary gain in amplitude (Fig. 4B).


The timing of the shrew: continuous melatonin treatment maintains youthful rhythmic activity in aging Crocidura russula.

Magnanou E, Attia J, Fons R, Boeuf G, Falcon J - PLoS ONE (2009)

Shrews' locomotor activity over the duration of the experiment.A: Actograms of a control and a melatonin-implanted shrew from the age of 12 to 30 months. Each line corresponds to one experimental day and there are 24 boxes per line (one box per hour). Nest exits are expressed as a grey scale: the darker the area, the higher the activity for a particular period. Blue arrows indicate each time a new implant was supplied. B: Daily activity profiles (mean±SEM) of controls (red) and melatonin-implanted (blue) shrews at, respectively, 12, 17, 21 and 30 months after the beginning of the experiment. Shrews were submitted to a natural light–dark regime. Grey boxes correspond to the night. Due to mortality, the number of individuals decreased during the experiment so that n was 11, 9, 6 and 4 at respectively month 12, 17, 21, and 30.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2690841&req=5

pone-0005904-g003: Shrews' locomotor activity over the duration of the experiment.A: Actograms of a control and a melatonin-implanted shrew from the age of 12 to 30 months. Each line corresponds to one experimental day and there are 24 boxes per line (one box per hour). Nest exits are expressed as a grey scale: the darker the area, the higher the activity for a particular period. Blue arrows indicate each time a new implant was supplied. B: Daily activity profiles (mean±SEM) of controls (red) and melatonin-implanted (blue) shrews at, respectively, 12, 17, 21 and 30 months after the beginning of the experiment. Shrews were submitted to a natural light–dark regime. Grey boxes correspond to the night. Due to mortality, the number of individuals decreased during the experiment so that n was 11, 9, 6 and 4 at respectively month 12, 17, 21, and 30.
Mentions: All individuals, aged 11–15 mo, displayed a marked diel activity rhythm, which was the highest during the first half of the night (expressed as the number of nest exits per hour) (Fig. 3). A secondary smaller peak was observed early during the light phase (Fig. 3). This bimodal pattern had a marked 24 h periodicity of high amplitude. After month 15, the amplitude of the rhythm decreased dramatically in both controls and sham-implanted shrews, and was no longer observed after month 17 (Figs 3, 4). In parallel, the significance of the 24 h period also decreased to the point where it was no longer discernable (Figs 3, 4). In contrast, in the implanted animals (i) the first noticeable decrease in amplitude of the rhythm was delayed by 3 months and (ii) the 24 h period remained highly significant until death (Figs 3, 4). In addition, the second and, to a lesser extent, the third implants induced a temporary gain in amplitude (Fig. 4B).

Bottom Line: Senescence is associated with a broad suite of physiological changes, including a decreased responsiveness of the circadian system.In both, a marked diel rhythm (low diurnal concentration; high nocturnal concentration) was present in young animals but then decreased in adults, and, as a result of a loss in the nocturnal production, was absent in old animals. 2) Daily locomotor activity rhythm was monitored in pre-senescent animals that had received either a subcutaneous melatonin implant, an empty implant or no implant at all.This is the first long term study (>500 days observation of the same individuals) that investigates the effects of continuous melatonin delivery.

View Article: PubMed Central - PubMed

Affiliation: UPMC University of Paris 06, UMR 7628, Banyuls/Mer, France. elodie.magnanou@obs-banyuls.fr

ABSTRACT

Background: Laboratory conditions ify the extrinsic factors that determine the wild expected lifespan and release the intrinsic or potential lifespan. Thus, wild animals reared in a laboratory often show an increased lifespan, and consequently an increased senescence phase. Senescence is associated with a broad suite of physiological changes, including a decreased responsiveness of the circadian system. The time-keeping hormone melatonin, an important chemical player in this system, is suspected to have an anti-aging role. The Greater White-toothed shrew Crocidura russula is an ideal study model to address questions related to aging and associated changes in biological functions: its lifespan is short and is substantially increased in captivity; daily and seasonal rhythms, while very marked the first year of life, are dramatically altered during the senescence process which starts during the second year. Here we report on an investigation of the effects of melatonin administration on locomotor activity of aging shrews.

Methodology/principal findings: 1) The diel fluctuations of melatonin levels in young, adult and aging shrews were quantified in the pineal gland and plasma. In both, a marked diel rhythm (low diurnal concentration; high nocturnal concentration) was present in young animals but then decreased in adults, and, as a result of a loss in the nocturnal production, was absent in old animals. 2) Daily locomotor activity rhythm was monitored in pre-senescent animals that had received either a subcutaneous melatonin implant, an empty implant or no implant at all. In non-implanted and sham-implanted shrews, the rhythm was well marked in adults. A marked degradation in both period and amplitude, however, started after the age of 14-16 months. This pattern was considerably delayed in melatonin-implanted shrews who maintained the daily rhythm for significantly longer.

Conclusions: This is the first long term study (>500 days observation of the same individuals) that investigates the effects of continuous melatonin delivery. As such, it sheds new light on the putative anti-aging role of melatonin by demonstrating that continuous melatonin administration delays the onset of senescence. In addition, the shrew appears to be a promising mammalian model for elucidating the precise relationships between melatonin and aging.

Show MeSH
Related in: MedlinePlus