Melatonin or a melatonin agonist corrects age-related changes in circadian response to environmental stimulus

The effects of a melatonin agonist, S-20098, included in the diet were tested on a specific effect of aging in hamsters: the marked decline in the phase shifting effects of a 6-h pulse of darkness on a background of constant light. In contrast to young hamsters, old hamsters fed with the control diet showed little or no phase shifts in response to a dark pulse presented in the middle of their inactive or active period. Old hamsters fed with S-20098 showed phase shifts that were ~70% of the ones in young animals and significantly greater than those in old controls. The phase advancing response to a dark pulse presented during the inactive period was dose dependent and reversed after S-20098 discontinuation. Melatonin included in the diet showed comparable restorative effects on the phase shifting response to a dark pulse in old hamsters. Replacement therapy with melatonin or melatonin-related compounds could prove useful in treating, preventing, or delaying disturbances of circadian rhythmicity and/or sleep in older people.