Apoptosis and Aging in Drosophila

Abstract

Several genes involved in the regulation of apoptosis can influence longevity. Although observations in several different systems imply that apoptosis and aging are closely linked, the relationship between the two remains largely unknown. In this study, Drosophila melanogaster was used as a model organism to explore the relationship between aging and apoptosis regulation. Apoptosis was investigated using two apoptotic hallmarks: caspase activity and DNA fragmentation. The results showed that apoptosis occured in adult flies at all ages and the changes in apoptosis associated with aging were linked to physiological age and were tissue-specific. During normal fly aging, apoptosis increased gradually within the muscle and was activated in the fat of old flies. However, neither of the two apoptotic signs were shown in the nervous system. The analysis of the apoptotic response to starvation and oxidative stress suggested that the increased apoptosis in muscle resulted from the accumulation of oxidative damage associated with aging. Once the presence of apoptosis during Drosophila aging was confirmed, the expression of anti-apoptotic genes was manipulated in specific tissues to examine the impact of a localized alternation of apoptosis on aging. The overexpression of anti-apoptotic genes in muscle extended Drosophila mean and maximum life span up to 99% and 65%, respectively. This extension was mediated by apoptosis inhibition using the detection of caspase activity and DNA fragmentation. In addition, the long-lived animals exhibited increased resistance to oxidative stress and preserved flight ability. Overall this study establishes that muscle apoptosis limits life span and participates in sarcopenia. This finding may have applications in the development of interventions to improve the life quality of elderly human.