Asymmetric segregation of protein aggregates is associated with cellular aging and rejuvenation

Abstract

Aging, defined as a decrease in reproduction rate with age, is a fundamental characteristic of all living organisms down to bacteria. Yet we know little about the causal molecular mechanisms of aging within the in vivo context of a wild-type organism. One of the prominent markers of aging is protein aggregation, associated with cellular degeneracy in many age-related diseases, although its in vivo dynamics and effect are poorly understood. We followed the appearance and inheritance of spontaneous protein aggregation within lineages of Escherichia coli grown under nonstressed conditions using time-lapse microscopy and a fluorescently tagged chaperone (IbpA) involved in aggregate processing. The fluorescent marker is shown to faithfully identify in vivo the localization of aggregated proteins, revealing their accumulation upon cell division in cells with older poles. This accretion is associated with >30% of the loss of reproductive ability (aging) in these cells relative to the new-pole progeny, devoid of parental inclusion bodies, that exhibit rejuvenation. This suggests an asymmetric strategy whereby dividing cells segregate damage at the expense of aging individuals, resulting in the perpetuation of the population.ibpA ͉ inclusion bodies ͉ protein aggregation ͉ small heat-shock protein

Specification and Simulation of Synthetic Multicelled Behaviors

“…Each state of the program specifies a growth rate, a reporter protein, and whether to emit a given signal. Transitions occur either upon cell division, in which case they are mother-daughter 35 specific, or after timers have elapsed. In state 1, the cell grows at a rate of 0.01 fL/min.…”

Regulation of mean and noise of the in vivo kinetics of transcription under the control of the lac/ara‐1 promoter

“…It is unknown to what extent they apply in vivo. For one, cells are not well-stirred [20]. Also, the DNA structure may differ, among other possible differences.…”

Spontaneous self-assembly of pathogenic huntingtin exon 1 protein into amyloid structures

“…Cells left with IBs show a reduced capacity for reproduction, suggesting that they experience increased cellular stress [7]. As neurons are post-mitotic cells, they are constantly exposed to IBs and thus to proteotoxic stress.…”

“…Differentiated postmitotic neurons seem significantly more vulnerable to proteins with pathogenic polyQ tracts than fast-dividing mitotic cells. The molecular basis for the selective degeneration of neuronal cells in polyQ diseases, however, is still unclear [7].…”