Naslov
A single-stage mechanism controls replicative senescence through Sudden Senescence Syndrome

Autori
Rubelj, Ivica ; Huzak, Miljenko ; Brdar, Branko ; Pereira-Smith, Olivia

Izvornik
Biogerontology (1389-5729) 3 (2002), 4; 213-222

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
abrupt telomere shortening; aging; crisis; fibroblasts; M1/M2; senescence; SV40 Tg; telomeres; telomere loop

Sažetak
Normal human cells have a finite proliferative potential in vitro. However, some DNA viral proteins, such as SV40 Tg, can alter this and extend the lifespan after which the cells enter crisis, a period when massive cell death occurs. Based on these observations, a two-stage model for cellular senescence has been proposed with a distinct function for each stage. Mortality stage 1 (M1) is hypothesized to cause cell senescence and is activated near the end of the proliferative lifespan, whereas Mortality stage 2 (M2) involves an independent mechanism that causes failure of cell division and crisis. Here, we present experimental evidence demonstrating that inhibition of the onset of Sudden Senescence Syndrome (SSS) by SV40 Tg greatly reduces the appearance of senescent cells in the culture and results in an increase in the population doublings (PD) to that of the number of cell generations (CGs). This is what causes the observed lifespan extension. Our results also provide an explanation for 'additional' telomere shortening during this 'extended' lifespan. Based on these observations, we suggest that crisis or M2 cannot be considered a 'mechanism' controlled by a specific set of genes. Our results do not support the previously proposed two-stage model and indicates SSS as the single, primary mechanism of cell senescence. Several recent findings from other laboratories that support our previously published self-recombination model of the molecular mechanisms that control SSS are discussed.

Izvorni jezik
Engleski

Znanstvena područja
Matematika, Biologija

POVEZANOST RADA