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Systems biology of the individual stochastic timer of aging

Project description

Turning back the clock on aging

Is there a way to reverse the body’s biological age? Why do genetically identical organisms raised in the same conditions get sick and die at different times? These are the questions the EU-funded AgingTimer project will answer. Specifically, it considers aging to be a major risk factor for incapacity and demise. Therefore, it will identify the stochastic timer of aging and develop methods to decipher the timer in order to eventually turn it back. For instance, it will use systems biology to mathematically define the stochastic timer of aging and it will study the neurobiology of behavioural individuality. The project will also address both molecular and social factors that differ between individuals by studying socioeconomic status in humans and social ranking in mice.

Objective

Aging is the biggest risk factor for frailty and death. However, we lack basic understanding of a fundamental question: Why do genetically identical organisms raised in the same conditions get sick and die at different times? If we understood the stochastic timer that drives aging in each individual, we could devise ways to turn back the timer and treat age-related diseases, extending the healthy lifespan. This requires addressing both molecular and social factors that vary between individuals, such as socioeconomic status in humans and social ranking in mice, which impact every aspect of aging. This synergy program aims to identify the stochastic timer of aging and develop methods to read the timer and turn it back. We use mice as a tractable organism relevant to human aging, and combine three disciplines: 1) systems biology to mathematically define the stochastic timer of aging and the basic concepts needed to understand its production, removal and noise processes; 2) neurobiology of behavioral individuality; and 3) biology of cellular senescence, which studies the most promising candidate for the timer: senescent cells that accumulate with age, causing chronic inflammation and whose removal delays age-related decline. To pinpoint the timer, we will follow the natural variability of large cohorts of genetically identical mice, tracked across the lifespan by video and RFID tags. We will measure a battery of behavioral, physiological and molecular parameters, as well as senescent cells in multiple organs throughout life. We will use new mouse models that allow us to visualize, pull down and ablate senescent cells, to provide full molecular profiles of senescent cells in different organs and to characterize their immune-surveillance mechanisms. This study will provide basic understanding of the timer of aging and provide ways to read the timer. Moreover, we will offer new ways to set back the timer in order to address age-related diseases and functional decline.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-SyG - Synergy grant

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Call for proposal

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(opens in new window) ERC-2019-SyG

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Host institution

WEIZMANN INSTITUTE OF SCIENCE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 8 687 500,00
Address
HERZL STREET 234
7610001 Rehovot
Israel

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 8 687 500,00

Beneficiaries (1)

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