Abstract：
:In this paper, we approach the problem of attempting to understand senescence by understanding the complexity and hierarchical structure of mammalian organisms. To do this, we make use of some concepts from abstract relational biology; in particular, graph theory. We subsequently utilize these concepts to develop the idea of an irreplaceable element in a mammalian system. We then make use of these elements, and some concepts from reliability theory, to show how senescence processes in mammalian systems may be related to the failure of a critical number of irreplaceable elements. Finally, we show how we may derive formulas for the expected number of elements which fail by a given time, and how this time is related to actual lifespan and expected lifespan of the organism. In particular, we relate this to some recent work by Cutler on the evolution of longevity.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Witten Mdoi
10.1016/0047-6374(84)90056-3subject
Has Abstractpub_date
1984-10-31 00:00:00pages
323-40issue
3eissn
0047-6374issn
1872-6216pii
0047-6374(84)90056-3journal_volume
27pub_type
杂志文章abstract：:Elderly people are at risk from an increased incidence of infections. Therefore we have studied the correlation between the production of several immunological parameters such as interferon-gamma (IFN-gamma), interferon-alpha-2 (IFN-alpha-2), interleukin-2 (IL-2), soluble interleukin-2 receptors (sIL-2R) and interleuk...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(93)90066-z
更新日期：1993-08-01 00:00:00
abstract：:During senescence, autofluorescent lysosomal storage bodies known as lipofusin or age pigment accumulate in many post-mitotic types of cells. Among these cell types is the retinal pigment epithelium (RPE) of the mammalian eye. The mechanisms of lipofuscin formation and accumulation have been studied more extensively i...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2004.11.004
更新日期：2005-04-01 00:00:00
abstract：:The results of this study show that an isogeneic barrier to the successful adoptive immunotherapy of Mycobacterium tuberculosis infected mice is progressively lost as these animals age. This was shown in this study by the demonstration that increasing levels of transferred acquired specific resistance could be conferr...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(88)90111-x
更新日期：1988-12-01 00:00:00
abstract：:DNA-repair capacity, by incorporation in vitro of [3H]thymidine into DNA of isolated neuronal cells and splenic lymphocytes of rat was studied as a function of age. The incubations were carried out both in the presence and absence of hydroxyurea (HU), a known inhibitor of replicative DNA synthesis. The results indicat...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(91)90053-3
更新日期：1991-03-01 00:00:00
abstract：:Researchers and clinicians interested in human diseases of DNA repair deficiency and premature aging gathered at the National Conference Center in Lansdowne, Virginia on 5-8 September 2006 to attend a workshop co-organized by Vilhelm Bohr (National Institute of Aging) and Kenneth Kraemer (National Cancer Institute). A...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2006.11.028
更新日期：2007-02-01 00:00:00
abstract：:Age-specific mortality rates from stomach cancer (SC) in Japan from 1950 through 1993 were subjected to longitudinal Gompertzian analysis. Age-specific SC mortality rate distributions between ages 45 and 75 years were highly Gompertzian for each- and every year for both men and women. Between 1950 and 1993, age-adjust...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(95)01669-4
更新日期：1995-11-24 00:00:00
abstract：:Published data on age-related human biological functions are surveyed. For the many showing a linear decrease, regressions were calculated, or existing functions extrapolated, to yield an intercept on the abscissa. The values of chi(0), the age at which a function ceases, provide a tentative common means of comparison...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/0047-6374(93)90072-y
更新日期：1993-06-01 00:00:00
abstract：:Chondrocytes derived from chick embryos can be successfully implanted in defects of adult chick articular cartilage surfaces. Such implants thrive in their implantation site and create a new articular surface. The chondrocytes mature and hypertrophy in the orthotopic site without invoking an immune response. Eventuall...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(89)90060-2
更新日期：1989-10-01 00:00:00
abstract：:The occurrence of inactive enzyme molecules in a variety of tissues and animal species has been shown to be of a general nature. The levels of inactive enzyme molecules found in old animals were produced by amino acid analogs in young animals. These levels have been shown to be initially detrimental but subsequently t...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/0047-6374(79)90098-8
更新日期：1979-02-01 00:00:00
abstract：:The present study examined the effect of a 40% reduction in caloric intake (CR) versus ad libitum (AL) feeding on retinal aging. CR- and AL-fed Brown Norway (BN) rats were obtained at 12, 24 and 30 months of age from the National Center for Toxicological Research (NCTR). Age-dependent declines in outer nuclear layer (...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(00)00096-8
更新日期：2000-03-13 00:00:00
abstract：:Developments in medicine have led to a significant increase in the average human lifespan. This increase in aging is most readily apparent in the case of HIV where antiretroviral therapy has shifted infection from a terminal to a chronic but manageable disease. Despite this advance, patients suffer from co-morbidities...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2018.07.008
更新日期：2018-10-01 00:00:00
abstract：:To investigate age-related changes in gene expression in WI-38 cells, we isolated RNA from young and senescent, quiescent cultures and made subtracted cDNA libraries. Density-arrested cells were incubated in serum-free MCDB-104 for 3 days. RNA was then isolated and subtracted cDNA libraries were made in the phagemid v...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(92)90039-g
更新日期：1992-09-01 00:00:00
abstract：:To gain insight into the anti-ageing mechanisms of caloric restriction (CR), liver mitochondria were isolated from male Brown-Norway rats of different ages (fully fed control and CR) and various specific markers of non-enzymatic protein modification (by oxidative, glyco- and lipoxidative-reactions) were measured by GC...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2004.06.002
更新日期：2004-08-01 00:00:00
abstract：:The proto-oncogene c-fos (the cellular homolog of v-fos, Finkel-Biskis-Jenkins (FBJ) murine osteogenic sarcoma virus) encodes a major component of the activator protein-1 (AP-1) transcription factor. Serum stimulation as well as oxidizing treatments induce transitory increases in c-fos mRNA abundance. The induction of...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(95)01689-9
更新日期：1996-03-29 00:00:00
abstract：:Food restriction increases maximal life span in rodents. Male rats that exercise in voluntary running wheels do not have an increase in maximal longevity despite a relative caloric deficit. In contrast, sedentary rats that are food restricted so as to cause the same caloric deficit have an extension of maximal longevi...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(97)00140-1
更新日期：1998-02-16 00:00:00
abstract：:In this study, we showed that in flies kept for 2 weeks at 1 (terrestrial gravity), 3 or 5 x g (hypergravity, HG) before transfer to 1 x g, resistance to heat remained higher in HG flies for several weeks after the transfer. The measurement of heat shock protein 70 (hsp70) indicated no induction of the protein in HG, ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(99)00024-x
更新日期：1999-06-01 00:00:00
abstract：:Changes in activity of some hepatic enzymes related to UDP-glucuronic acid conjugation (UDP-glucose dehydrogenase and UDP-glucuronyl transferase) and glutathione-related enzymes (glutathione reductase and glutathione peroxidase) were investigated in male and female Wistar rats as a function of age. UDP-glucose dehydro...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(88)90084-x
更新日期：1988-08-01 00:00:00
abstract：:Following a 3 hour in vivo labelling of cytoplasmic RNA in rat liver with orotic acid-6-14C under conditions where ribosomal RNA synthesis was suppressed, the proportion of labelled messenger-like RNA released to the cytoplasm which contained polyadenylate (poly(A)) tracts was about 3.0 times higher in the livers of j...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(77)90026-4
更新日期：1977-07-01 00:00:00
abstract：:The age-dependent drop in mixed lymphocyte reactivity and responsiveness to concanavalin A of lymph node and spleen cells of C57Bl/6J female mice were studied. The relative decrease in mixed lymphocyte reactivity was shown to be the same whether mounted against H-2 or Mls incompatibile stimulator cells. The time of pe...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(79)90118-0
更新日期：1979-01-01 00:00:00
abstract：:A comparison was made of the resting membrane potential (MP) as well as the MP responses to K+, ACTH and gamma-MSH of superfused adrenocortical, zona fasciculata cells from young (Y) and old (O) male rats. The resting MP of these cells did not vary with age. However, the MP responses to altered extracellular [K+] vari...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(88)90036-x
更新日期：1988-06-01 00:00:00
abstract：:We used a fluorescence differential display--PCR (FDD-PCR) technique to analyze the genes expressed in mouse kidneys collected at nine different developmental stages ranging from 3 days to 15 months after birth. We found ten genes that were age-dependent and differentially-expressed in the kidneys during our experimen...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(99)00104-9
更新日期：2000-02-07 00:00:00
abstract：:To further explore whether immune function and acute phase response are altered during ageing, the response to a mild inflammatory stress (DT-Polio-Typhim vaccination) was studied in elderly and young subjects. Cytokine production (IFN-gamma, TNF-alpha, IL-6, IL-10) by whole blood cultures, circulating cytokines and a...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2005.03.008
更新日期：2005-08-01 00:00:00
abstract：:Here we show that a labyrinth channel compartment and slit diaphragms, which are the histological structures enabling insect nephrocytes ultrafiltration, are established during embryogenesis first by the garland nephrocytes (GCNs). The later pericardial nephrocytes, which represent the majority of functional nephrocyt...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2018.04.006
更新日期：2018-07-01 00:00:00
abstract：:There is now strong evidence implicating the generation of reactive oxygen species (ROS) and the corresponding response to oxidative stress as key factors in the pathogenesis of several human diseases including cancer, atherosclerosis, and neurodegenerative disorders, and in ageing. The carcinogenicity of oxidative st...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2006.01.021
更新日期：2006-05-01 00:00:00
abstract：:In yeast, increasing the copy number of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase Sir2 extends lifespan, which can be inhibited by nicotinamide (Nam), the end-product of Sir2-mediated NAD-breakdown. Furthermore, the yeast pyrazinamidase/nicotinamidase PNC-1 can extend yeast lifespan by converti...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2007.01.004
更新日期：2007-04-01 00:00:00
abstract：:There is currently of a great interest investigating the role of nutrition in the prevention of age-associated disorders. The present study aimed to evaluate, on a particular strain of mice, the efficacy of alternate-day fasting on the mitochondrial production of free radical species and on the incidence of a specific...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2005.06.007
更新日期：2005-11-01 00:00:00
abstract：:Protein synthetic activity was determined in postmitochondrial preparations from heart, brain, kidney, liver and skeletal muscle of 5-26-month-old female C57B1/6J mice. An age-dependent decrease in the rate of protein synthesis was exhibited by all preparations except heart muscle. A 65% decrease in translational rate...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(83)90051-9
更新日期：1983-03-01 00:00:00
abstract：:The lifespan of the nematode, Caenorhabditis elegans, can be extended by mutations affecting components of the insulin-like growth factor (IGF) signaling cascade or by overexpression of SIR2, an NAD+-dependent protein deacetylase. The mammalian homologue of SIR2, Sirt1, has been shown to modulate the activity of FoxO,...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2005.04.006
更新日期：2005-10-01 00:00:00
abstract：:Rats of two age groups (6 weeks and 30 months) received (1) a single dose of 600 mg D-galactosamine (GalN)/kg body weight by intraperitoneal (i.p.) injection, (2) a single dose of 600 mg GalN/kg body weight i.p. combined with 20 mg prednisolone/kg body weight subcutaneously at the beginning of the experiment. The kine...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(78)90064-7
更新日期：1978-03-01 00:00:00
abstract：:Werner syndrome (WS) is a premature aging and cancer-prone disease caused by loss of the RecQ helicase WRN protein. Cultured WS fibroblasts display high genomic instability and senesce prematurely. Epigenetic inactivation of the WRN gene occurs in numerous tumor types, in which WRN demonstrates tumor suppressor-like a...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2007.05.009
更新日期：2007-07-01 00:00:00
