Duration of senescent cell survival in vitro as a characteristic of organism longevity, an additional to the proliferative potential of fibroblasts

Yegorov, Yegor E.; Zelenin, A. V.

doi:10.1016/s0014-5793(03)00298-9

Cited by 23 publications

(8 citation statements)

References 56 publications

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“…45 The relative importance of telomere shortening, oxidative stress, and genomic stability in defining the proliferative capacity of cells is unclear and controversial. 46,47 Our results indirectly support the concept that HSCs (similar to other somatic cells) undergo a finite number of replications before cellular senescence. 48 Because mice, cats, and baboons can be ordered not only by longevity but also by size, we cannot rule out the possibility that the biologic mechanism that drives slower HSC-replication rates in primates is size.…”

supporting

confidence: 78%

Hematopoietic stem-cell behavior in nonhuman primates

Shepherd

Kiem

Lansdorp

et al. 2007

Blood

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Little is known about the behavior of hematopoietic stem cells (HSCs) in primates because direct observations and competitive-repopulation assays are not feasible. Therefore, we used 2 different and independent experimental strategies, the tracking of transgene expression after retroviral-mediated gene transfer (N ‫؍‬ 11 baboons; N ‫؍‬ 7 rhesus macaques) and quantitation of the average telomere length of granulocytes (N ‫؍‬ 132 baboons; N ‫؍‬ 14 macaques), together with stochastic methods, to study HSC kinetics in vivo. The average replication rate for baboon HSCs is once per 36 weeks according to gene-marking analyses and once per 23 weeks according to telomere-shortening analyses. Comparable results were derived from the macaque data. These rates are substantially slower than the average replication rates previously reported for HSCs in mice (once per 2.5 weeks) and cats (once per 8.3 weeks). Because baboons and macaques live for 25 to 45 years, much longer than mice (ϳ2 years) and cats (12-18 years), we can compute that HSCs undergo a relatively constant number (ϳ80-200) of lifetime replications. Thus, our data suggest that the self-renewal capacity of mammalian stem cells in vivo is defined and evolutionarily conserved. IntroductionHematopoiesis is the ordered process by which hematopoietic stem cells (HSCs) proliferate and differentiate into mature blood cells. Through replication and differentiation, HSCs generate clones of progenitors, precursors, and mature cells, which support hematopoiesis throughout an animal's life. HSCs cannot be directly observed and are generally defined and identified by their function (their ability to reconstitute and maintain hematopoiesis).The most informative experimental approach for studying HSC kinetics is limiting-dilution competitive-repopulation experiments. Small numbers of cells with distinguishable phenotypes are transplanted into a recipient animal in which hematopoiesis has been ablated. After the HSCs engraft and restore blood cell production, the percentage of marrow progenitor cells or blood granulocytes of each phenotype is tracked over time, because this reflects the phenotype of contributing (differentiating) HSC clones. 1,2 Using such data, the frequency of HSCs in mice and cats was estimated, as were their average replication and differentiation rates. [3][4][5] Importantly, the estimated frequency of HSCs in mice derived with stochastic analyses was similar to frequencies estimated with independent methods. [6][7][8][9] In addition, the results from transplantation studies overlapped the results from studies of unperturbed hematopoiesis, including 5-bromodeoxyuridine (BrdU)-labeling experiments. 6,9,10 Given the significant differences in estimates of the frequency of HSCs (number of HSCs/number of nucleated marrow cells; 4-8/10 5 vs. 6/10 7 ) and the average HSC-replication rate (once/2.5 weeks vs once/8-10 weeks) between mice and cats, we hypothesized that underlying biologic principles might explain these discrepancies. For example, our data and addit...

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supporting

confidence: 78%

Hematopoietic stem-cell behavior in nonhuman primates

Shepherd

Kiem

Lansdorp

et al. 2007

Blood

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“…In addition, the proliferative lifespans of fibroblasts were shown to decrease with aging, and fibroblasts derived from patients with syndromes of premature aging had reduced lifespans. 33,34) Therefore, the present finding of prolonged lifespan in HDF cells by cyanidin treatment suggests the possibility that cyanidin might prolong not only the lifespan of cells in vitro but also the longevity of organisms, although further study is needed to support this.…”

Section: Discussionmentioning

confidence: 72%

Anti-aging Effects of Cyanidin under a Stress-Induced Premature Senescence Cellular System

Choi

Kim

Park

et al. 2010

Biological & Pharmaceutical Bulletin

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Reactive oxygen species (ROS) including superoxide (O 2 Ϫ ), hydrogen peroxide (H 2 O 2 ), and hydroxyl radical ( · OH) are over-produced under pathological conditions and during the aging process. ROS can cause DNA strand breaks, base modifications, lipid peroxidation, and protein modifications, resulting in oxidative stress. Emerging evidence indicates that ROS are important risk factors in functional disorders or tissue injury related to the aging process. [1][2][3][4] According to the free radical theory of aging, the aging process is thought to lead to an imbalance between oxidative damage and antioxidative defense.5-9) Therefore, it has been suggested that the prevention of oxidative damage through the enhancement of antioxidative defense status may counteract aging and age-associated disorders such as cancer, 10) cardiovascular disorders, 11) and some neurodegenerative disorders.12) To delay the aging process through the attenuation of oxidative stress induced by excessive ROS, agents with antiaging effects have attracted much attention. In particular, anthocyanins are well known as antioxidants.13) Although the antioxidative effects of cyanidin, the most prevalent anthocyanin in the plant kingdom, [14][15][16] have been reported, its effects on aging and lifespan have not yet been studied.Although there are several experimental models for studying aging, human diploid fibroblasts (HDFs) have become a classic experimental model of cellular aging and are used to study aging-associated molecular changes in human cells. After serial passage, HDFs lose the ability to proliferate and become senescent, showing cellular changes related to the aging process, 17,18) termed replicative senescence (RS). In addition, HDFs exhibit the stress-induced premature senescence (SIPS) phenotype after being subjected to different sub-lethal stressors, including oxidative stress, 19,20) and this SIPS phenotype is almost identical to the phenotype associated with RS.20) The present study focused on the anti-aging activity of cyanidin and its related protective mechanisms against aging under SIPS using WI-38 human fibroblast cells. Furthermore, the effect of cyanidin on lifespan was also investigated. MATERIALS AND METHODSReagents Basal medium eagle (BME), paraformaldehyde, and Triton X-100 were purchased from Sigma Chemical Co. , and Nakalai (Kyoto, Japan), respectively. Monoclonal anti-cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), goat monoclonal anti-mouse immunoglobulin (IgG), and goat anti-rabbit IgG horseradish peroxidase-conjugated secondary antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, U.S.A.).Cell Culture and Treatment The WI-38 cells (human embryonic lung-derived diploid fibroblasts) were originally obtained from the ATCC (American Type Culture Collection, U.S.A.). WI-38 HDFs at population doubling levels (PDLs) of 26.0 were seeded at a density of 10 5 cells/ml in 6-or 96-well culture plates and incubated for 2 h. Three-hundred micromolars of H 2 O 2 was treated for 60 min ...

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“…However, a feedback-regulation should be in place to prevent cellular senescence from becoming irreversible (as is the case with terminal ageing of the organism), which, most of the time is independent of the initial stress conditions. The duration of cell survival in the non-dividing state after cessation of proliferation is also a characteristic of longevity [21]. The fate of senescent cells in the living organism is largely unknown.…”

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confidence: 99%

SIRT1 and AMPK in regulating mammalian senescence: A critical review and a working model

2010

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Edited by Wilhelm JustKeywords: Sirtuin LKB1 Aging Energy metabolism Stress a b s t r a c t Ageing in mammals remains an unsolved mystery. Anti-ageing is a recurring topic in the history of scientific research. Lifespan extension evoked by Sir2 protein in lower organisms has attracted a large amount of interests in the last decade. This review summarizes recent evidence supporting the role of a Sir2 mammalian homologue, SIRT1 (Silent information regulator T1), in regulating ageing and cellular senescence. The various signaling networks responsible for the anti-ageing and anti-senescence activity of SIRT1 have been discussed. In particular, a counter-balancing model involving the cross-talks between SIRT1 and AMP-activated protein kinase (AMPK), another stress and energy sensor, is suggested for controlling the senescence program in mammalian cells.

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Duration of senescent cell survival in vitro as a characteristic of organism longevity, an additional to the proliferative potential of fibroblasts

Cited by 23 publications

References 56 publications

Hematopoietic stem-cell behavior in nonhuman primates

Hematopoietic stem-cell behavior in nonhuman primates

Anti-aging Effects of Cyanidin under a Stress-Induced Premature Senescence Cellular System

SIRT1 and AMPK in regulating mammalian senescence: A critical review and a working model

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