Round 2 Results and collaboration with Hevolution

In June 2022 Impetus Grants concluded its second round and we are happy to finally share our results publicly. This round was unlike our previous open-ended effort as we aimed to fund labs that had ideas around addressing specific bottlenecks of the field - causality of methylation clocks, in vivo measurements of multiple aging mechanisms, interventional data in humans, and road mapping of open problems. In this round, we awarded 14 grants totaling $4 million to support groundbreaking scientific research across various disciplines and stages - from support to ideas with no preliminary data to ongoing clinical trials. 

The current round wouldn't be possible without our collaboration with Hevolution Foundation who generously agreed to match our funding, and the continuous support from our donors - Juan Benet, Michael Antonov, Vitalik Buterin, James Fickel, Jed McCaleb, Karl Pfleger, Fred Ehrsam, Molly Mackinlay, Feruell, and Gitcoin. 

Connecting genome-wide landscapes of DNA oxidation with multiple aging mechanisms in human blood

Dr. Vakil Takhaveev (ETH Zurich), Prof. Dr. Shana J. Sturla (ETH Zurich), Prof. Dr. Alejandro Ocampo (Université de Lausanne)

DNA damage has emerged as a key mechanism driving aging, yet there is no genome-wide data on how patterns of pervasive DNA damage products, such as oxidized nucleobases, evolve during aging or how they relate to other aging mechanisms. Only very recently has it become possible to create high-resolution genomic maps of DNA damage via customized sequencing library preparation protocols. In this collaboration, Dr. Takhaveev, Professor Sturla, and Professor Ocampo will work to decipher tandem patterns of oxidative DNA damage and DNA methylation across the human lifespan in blood samples, to uncover biomarkers at the interface of several aging hallmarks.

In situ genome-scale measurements of multiple aging mechanisms

Dr. William Allen, Professor Xiaowei Zhuang (Harvard University)

Professor Zhuang and Dr. Allen will combine spatially resolved single-cell transcriptomic and proteomic profiling to comprehensively map the molecular architecture of the aging brain and identify molecular and cellular signatures of aging. This project also aims to develop imaging-based pooled genetic screening methods to probe the molecular mechanisms underlying these aging signatures and identify molecular factors that can reverse aging.

Tracking protein lifetimes during aging with molecular recordings and nanopore peptide sequencing

Professor Jeff Nivala (University of Washington)

This project aims to develop a new protein recording technology, using a combination of genome editing and nanopore sequencing, to track protein lifetimes across cellular aging.

Protein Circuits to Enable Multiplexed Urinal Monitoring of Hallmarks of Aging

Professor Xiaojing Gao (Stanford University)

Gao Lab at Stanford aims to engineer biomolecular circuits that can convert a variety of aging biomarkers to outputs compatible with noninvasive, repetitive monitoring in animal models

The causal role of methylation in driving brain aging

Professor Hume Stroud (UT Southwestern)

Prof. Dr. Stroud will use mouse genetic tools to test the causal role of methylation in driving brain aging.

A comprehensive online compilation of open problems in longevity science

Professor Joao Pedro Magalhaes (University of Birmingham, UK)

In this project, Professor Pedro Magalhaes & team will create and populate an online framework of open problems in longevity and aging research. He will engage and collaborate with the scientific community to develop this project.

Geroprotective effects of rapamycin on inflammaging in older adults with periodontitis

Professor Jonathan An (University of Washington), Professor Vandana Kalia (Seattle Children's Research Institute)

The project will complete longitudinal immune profiling at a single-cell level in clinical trials of humans taking rapamycin.

Predict optimal rejuvenation cocktails with spatiotemporally resolved multi-omics and RNA velocity

Professor Jonathan Weissman (Whitehead Institute for Biomedical Research)

Recent advances have defined molecular hallmarks of aging and cocktails of transcription factors capable of reversing these changes. Unfortunately, we still lack a mechanistic understanding of how these rejuvenation treatments act or a means to systematically search for more potent and specific regimens. Here, Weissman lab will leverage the dynamo approach for mapping cell trajectories, which provides high-resolution spatial transcriptomics to predict optimal paths and cocktails that rejuvenate aged cells or delay the aging of youthful cells over time and space.

Identifying immunological correlates of frailty that diminish healthspan

Professor Alison Ringel (Ragon Institute)

Ringel Lab seeks to understand whether external measurements of aging are predictive for molecular deficits in the immune system that increase disease burden over time.

Evolutionary Selective Identification of Functional Human Age-related Changes in the DNA methylome

Professor Christopher Bell (Queen Mary University of London, UK)

The CpG dinucleotide can be considered a genome signaling unit – however, it must withstand strong genetic hypermutability compared to other genomic sequences.  This project will employ evolutionary and population genomic & epigenomic analysis to identify critical functionally important CpGs in the aging process.

NAD+ turnover dynamics in humans

Professor Lindsay Wu (University of New South Wales, Australia)

Nicotinamide adenine dinucleotide (NAD+) is a critical redox cofactor that declines with age and can be restored using NR or NMN. This decline with age only reflects a static, overall snapshot of total levels, which masks a hidden interplay between NAD+ synthesis and breakdown. The team will use isotope tracing of nicotinamide to obtain the first measurements of NAD+ synthesis and breakdown in humans, and whether either of these is altered by old age or exercise.

Multi-omic biomarkers and mechanistic insights from a clinical evaluation of rapamycin in women

Professor Yousin Suh, Professor Zev Williams (Columbia University)

In the previous Impetus grant round, two teams were awarded funding to conduct a double-blind, randomized, placebo-controlled trial to evaluate the ability of rapamycin to extend women’s reproductive health at Columbia University (PI, Zev Williams) and to reverse periodontal disease at the University of Washington (PI, Jon An). Leveraging these clinical trials, the team from Columbia University will conduct multi-omic analyses of clinical samples obtained from the same study population, with the goals of identifying robust biomarkers and deriving mechanistic insights from a clinical evaluation of rapamycin treatment for women’s health.

Clinical Evaluation of mTORC1 inhibition for Geroprotection: Biomarker Study

Professor Adam Konopka, Professor Dudley Lamming (University of Wisconsin-Madison)

This Phase 2, double-blind, clinical trial aims to identify how mTORC1 inhibition influences physiological and molecular hallmarks of aging across multiple tissues and systems. The team also aims to determine if proposed biomarkers of aging are amenable to mTORC1 inhibition and identify key biomarkers for future geroscience-guided phase 3 clinical trials.

Uncovering associations between hallmarks of aging, aging phenotypes, and age-related diseases

Dr. Rafael de Cabo (National Institute on Aging)

Developing aging biomarkers with data collected from Study of Longitudinal Aging in Mice (SLAM).