Biomedical subjects

João F Passos

Publications and source records attributed to João F Passos.

5 recordsLinked to original sources

PubMed2006

Oxygen free radicals in cell senescence: are they signal transducers?

Oxygen free radicals have a major impact on senescence of primary human cells. In replicative senescence, which is induced by uncapping of telomeres, the rate of telomere shortening is largely determined by telomere-specific accumulation of DNA damage induced by reactive oxygen species (ROS). More intense ROS-generating stressors can induce premature senescence via generation of telomere-independent DNA damage. Interestingly, ROS levels were also elevated when premature senescence was triggered by pathways downstream or independent of DNA damage. This has led to the suggestion that ROS generation could be a specific component of the signalling pathways inducing senescence. However, the available data are compatible with the concept that senescence is triggered as a DNA damage response. ROS appear to be involved as inducers of DNA damage rather than as specific signalling molecules. The upregulation of ROS production often seen in premature senescence might be related to retrograde response initiated by mitochondria.

Cellular Senescence↗

PubMed2006

Mitochondrial dysfunction and cell senescence: cause or consequence?

The mitochondrial theory of aging remains to date one of the most popular theories of aging. One major model of aging is replicative senescence, where the irreversible loss of division potential of somatic cells occurs after a more or less constant number of cell divisions. Few data are available concerning the role of mitochondria in this model. Here, we review evidence supporting the involvement of mitochondria in replicative senescence and a possible link to telomere biology. Moreover, we suggest that this process might be more complex than originally formulated, because variations in nuclear gene expression involved in mitochondrion nucleus cross-talk are observed in both senescence and immortalization.

Aging↗

PubMed2006

Extended lifespan and long telomeres in rectal fibroblasts from late-onset ulcerative colitis patients.

OBJECTIVES: Ulcerative colitis (UC) is characterized by damage to the intestinal epithelium and connective tissue. The causes of this damage could include changes in the ability of colonic fibroblasts to heal wounds and maintain epithelial cell proliferation. Telomeres shorten with each cell division and eventually signal senescence. The aim of this study is to investigate whether the impaired function of rectal fibroblasts in UC is due to accelerated telomere shortening, oxidative stress and premature senescence. METHODS: We isolated rectal fibroblasts from eight UC patients and nine non-colitis controls, and recorded their in-vitro lifespans. Telomere lengths and superoxide dismutase mRNA expression were also measured by real-time polymerase chain reaction and peroxide levels were measured by flow cytometry. RESULTS: The fibroblast lifespan decreased as patient age increased (R2=0.68, P=0.003) in control patients, but this relationship was absent in UC fibroblasts. We identified a group of patients who were diagnosed later in life than a second group (59 versus 35 years, P=0.002). Fibroblasts from these late-onset UC patients underwent significantly more population doublings before senescence than age-matched controls (25 versus 15, P=0.02). Slower in-vitro telomere shortening rates (32 versus 344, P=0.006) and trends towards longer telomeres at explant were also observed in late-onset UC fibroblasts. Peroxide levels correlated positively with telomere shortening rate (r=0.581, P=0.078). CONCLUSIONS: Some UC-predisposed individuals may have more efficient antioxidant systems that protect the telomeres from oxidative damage. This may allow their rectal fibroblasts to live longer, function better and thus delay the onset of the disease until later life.

Adult↗

PubMed2005

Mitochondria, telomeres and cell senescence.

The accumulation of oxidative damage is one of the most widely accepted causes of ageing. Mitochondrial dysfunction, in particular damage to the mitochondrial DNA has been hypothesised, more than thirty years ago, as responsible for increased production of reactive oxygen species (ROS) and, thus, as one possible causal factor for ageing. There is now a wealth of data that supports this hypothesis, which is mostly derived from models considering the ageing of post-mitotic or slowly dividing cells in vivo. One major cellular model of ageing, however, is replicative senescence, the irreversible loss of division potential of somatic cells after a more or less constant number of cell divisions. Not much data exists concerning the role of mitochondria in this model. Here, we review evidence supporting an involvement of mitochondria in replicative senescence and a possible link to telomere shortening.

Cell Division↗

PubMed2003

Strain PM2, a novel methylotrophic fluorescent Pseudomonas sp.

A novel bacterial strain, PM2, capable of growing on methanol, was isolated in alkaline conditions from a soil inoculum. This bacterium was characterized at the physiological, biochemical and molecular level. Based on biochemical and molecular data strain PM2 was classified as a novel member of the group of fluorescent pseudomonads. Evidence for the presence of a pyrroloquinoline quinone (PQQ)-linked alcohol dehydrogenase in this organism is presented. Strain PM2 is, to our knowledge, the first example of a methylotrophic Pseudomonas to be characterized in detail. This novel type of metabolism in Pseudomonas broadens even further the metabolic versatility for which this genus is renowned.

Alcohol Oxidoreductases↗