Chronic treatment of Syrian hamsters with low-dose selegiline increases life span in females but not males.
The only intervention conclusively shown to prolong life span in mammals is caloric restriction. Selegiline, a selective, irreversible inhibitor of monoamine oxidase B (MAO-B), is the first drug reported to reproducibly increase mean and maximum life span in animals, although this has only been demonstrated in male rats and mice. The effect on life span is commonly assumed to depend on MAO-B inhibition, but final experimental proof is missing. Therefore, we investigated the possible relationship between selegiline's effect on life span and MAO-B by monitoring survival data and MAO activity in Syrian hamsters of both sexes. Selegiline (0.05 mg/kg) significantly increased life span in female Syrian hamsters, but not in males. In contrast, MAO-B was inhibited equally in both sexes by about 40%, although females had a higher baseline MAO-B activity. No increase in MAO-B with age was observed. Female control hamsters had a shorter life span than male controls. Interestingly, this sex difference disappeared in the selegiline-treated animals. These findings suggest that the increase of life span by selegiline might be independent of MAO-B inhibition, but is possibly related to mechanisms determining sex differences of life span.
Stoll
S
S
Central Institute of Mental Health, Department of Psychopharmacology, Mannheim, Germany.
Hafner
U
U
Kränzlin
B
B
Müller
W E
WE
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D006224:Cricetinae; D005260:Female; D007700:Kinetics; D008017:Life Expectancy; D008297:Male; D008647:Mesocricetus; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology*; D012727:Sex Characteristics; D013534:Survival
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D008995:Monoamine Oxidase