Do antioxidant strategies work against aging and age-associated disorders? Propargylamines: a possible antioxidant strategy.
The free radical theory of aging was initially proposed by Harman half a century ago primarily to explain biological aging processes. Although administration of so-called antioxidant chemicals, which have been tested in the past for several decades, turned out to be mostly ineffective in prolonging the life spans of animals, the same theory of age-associated diseases appears to be increasingly supported in the last two decades. Despite these difficulties, the success in extending life span of 4 different animal species (mice, rats, hamsters, and dogs) with (-)deprenyl (including a study of our group) indicates that there might exist another type of antioxidant strategy in addition to a simple administration of antioxidant chemicals. (-)Deprenyl has also been shown to increase superoxide dismutase (SOD) and catalase (CAT) activities selectively in brain dopaminergic tissues. Interestingly, we have recently shown that another propargylamine, rasagiline not only increases antioxidant enzyme activities (CAT and SOD) in brain dopaminergic regions as (-)deprenyl does, but also increases CAT and SOD activities in extrabrain catecholaminergic systems such as the heart and kidneys as well. These recent observations coupled with previous observations on the life span of animals with (-)deprenyl suggest that pharmacological modulation of endogenous antioxidant enzyme activities could be one potential antioxidant strategy against aging and age-associated disorders. If the causal relationship between the two effects of (-)deprenyl exists as we hypothesized, we might be able to advance the elucidation of mechanism(s) of aging based on the free radical theory of aging.
Kitani
K
K
National Institute for Longevity Sciences, Obu, Aichi, Japan. kitani@nils.go.jp
Minami
C
C
Yamamoto
T
T
Maruyama
W
W
Kanai
S
S
Ivy
G O
GO
Carrillo
M C
MC
D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000480:Alkynes / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D002374:Catalase / Q000096:biosynthesis* / Q000235:genetics; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D006224:Cricetinae; D004285:Dogs; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005609:Free Radicals; D006321:Heart / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects; D008136:Longevity / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009928:Organ Specificity; D051381:Rats; D011916:Rats, Inbred F344; D012642:Selegiline / Q000494:pharmacology / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics
D000480:Alkynes; D000975:Antioxidants; D005609:Free Radicals; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C402679:N-2-heptyl-N-methylpropargylamine; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C031967:rasagiline; D012642:Selegiline; D002374:Catalase; D013482:Superoxide Dismutase; D004298:Dopamine