Towards the whole-cell model of yeast replicative ageing

Cellular ageing is a complex multifactorial process affected by an intertwined network of effectors such as protein translation, protein quality control, mitochondrial dysfunction, and metabolism.

Using systems biology approaches, we will understand the major regulators of lifespan and identify critical events contributing to cellular senescence by (1) establishing a large-scale mechanistic model of nutrient signalling, (2) building a multiscale whole-cell model to understand how longevity pathways and metabolic status impact maintenance of the proteome in both young and old yeast cell during replicative ageing and (3) identify how critical cellular events responsible for lifespan regulation are orchestrated.

The proposed project is estimated for 4-years, starting in 2024, and it will be led by me.

PhD student will be hired and will start in 2024 with the large-scale kinetic model of nutrient-sensing pathways (Aim 1). Multiscale model (Aim 2), and data sampling will be performed during 2025 and 2026. Application of models (Aim 3) is scheduled from mid-2026 until 2027.

This project will shed light on the importance of nutrient availability and metabolism in regulating lifespan and will provide novel avenues for increasing health span.

It also might open new opportunities in precision medicine by optimization of metabolism to promote repair and by developing interventions which delay the onset of multiple chronic, age-related diseases by targeting the metabolic pathways.