Inhibition of H₂O₂‐induced apoptosis of lymphocytes by calorie restriction during aging

Abstract

Calorie restriction (CR) is known to delay the aging process in rodents and is postulated to act by decreasing free radical generation and increasing antioxidant enzyme activity. The present study was designed to investigate the effect of CR and age on oxidative stress-induced apoptosis and associated changes in the levels of TNF-alpha, and Bcl-2 in splenic T lymphocytes. Ad libitum (AL)- or CR-fed C57BL/6J mice were sacrificed either at 6 (young) or 18 (old) months and splenic lymphocytes were incubated with or without 25 micro M H2O2 to induce apoptosis. Apoptosis increased with age in cells of AL-fed mice incubated with H2O2. CR prevented this rise in apoptosis in total splenic lymphocytes and in CD4(+) and CD8(+) T lymphocyte subsets either with or without H2O2. Free radicals increased and mitochondrial membrane potential decreased in aged mice. CR prevented these changes and also prevented the age-associated increase in TNF-alpha and loss of Bcl-2 in total splenic lymphocytes and in CD4(+) and CD8(+) lymphocyte subsets. In summary, lymphocytes in aged AL-fed mice were much more susceptible to oxidative stress-induced apoptosis whereas CR normalized apoptosis by preventing the increase in TNF-alpha and the decrease in Bcl-2 associated with aging.

Apoptosis of CD4+ T and Natural Killer Cells in Alzheimer's Disease

“…In addition, a positive correlation was observed for B cells and for CD4 + T lymphocytes when plotting Bcl2 content versus percentage of apoptotic cells. Reduction of Bcl2 in both T cell subsets as been reported in aging [1,3,18], however, CD8 T cells appear to be notably affected [59]. In general, CD8 + cells seem to play a pivotal role in aging [14,46].…”

Survivin expression increases during aging and enhances the resistance of aged human fibroblasts to genotoxic stress

“…Indeed, fibroblasts cultured from old individuals were more sensitive to H 2 O 2 -induced apoptosis than those cultured from younger ones (Miyoshi et al 2006). Apoptosis also increased with age in cells of AL-fed mice incubated with H 2 O 2 (Avula and Fernandes 2002). These discrepancies are probably due to the use of different species, different strains, or different cell types (Higami and Shimokawa 2000).…”

Impact of Age, Caloric Restriction, and Influenza Infection on Mouse Gut Microbiome: An Exploratory Study of the Role of Age-Related Microbiome Changes on Influenza Responses

“…Nonetheless, CR has consistently shown improvement in multiple facets of aging, including delaying immunosenescence ( 33 – 37 ). Most notably, CR attenuates the shift from naive to memory phenotype observed in T cells with aging ( 38 ) and maintains the proliferative capacity of T cells ( 39 , 40 ). Despite these positive effects on the aged immune system, the effects of CR on immune responses to influenza with aging is not clear.…”