Longevity research

Autophagy Activator Drug Discovery Platform

Ageing is associated with the decline in the capacity of the autophagy pathway to degrade dysfunctional and damaging cellular components, such as protein aggregates and mitochondria. Dysfunctional autophagy, in turn, undermines other cellular functions including DNA repair, metabolism and survival. Therefore, activation of autophagy is considered a promising therapeutic approach to combat ageing and age-related diseases. A large number of screens has been performed and published to date, these have identified a wide range of small molecules that stimulate initiation of autophagy. Prof. Korolchuck lab proposes to initiate a drug discovery program with the aim of identifying novel bioactive autophagy inducers.

ApoptoSENS - Senolytic CAR-NK Cells

Background Cellular senescence is the irreversible arrest of proliferation associated with a proinflammatory phenotype that can lead to tissue dysfunction and is implicated in numerous diseases. Natural Killer cells have an innate ability to remove senescent cells, however immune evasion can occur, which contributes to an accumulation of senescent cells with age. Several genetic and pharmacological studies have shown that elimination of senescent cells can ameliorate hallmarks of aging in both mice and humans, however more specific therapeutic interventions are required. ‍Aims, Hypothesis & Results ‍Dr. Amit Sharma is developing Chimeric Antigen Receptor Natural Killer (CAR-NK) cells to precisely and safely eliminate senescent cells in vivo. The team have identified a number of senescence-specific surface markers which could be targeted for senescence removal. They will focus on their most promising candidate senescent cell markers which will be more extensively validated using additional cell model paradigms (stressors), as well as in mouse models (cross-species validation). Validated surface markers will be used to generate monoclonal antibodies, which will then be confirmed for specificity against the target antigen. Appropriate CAR-NK cells will be created to further establish proof-of-concept for their approach of selective removal of senescent cells in their various model systems. Timeline The Sharma Lab will target the senescent cells they have identified by generating monoclonal antibodies against their senescence-specific surface markers. These monoclonal antibodies will then be used to create CAR-NK cells that can selectively eliminate senescent cells. Pre-clinical studies ‍Required Funding: $430,000 Duration: 24 Months VitaDAO Board Evaluation Writeup Dr. Amit Sharma has a strong scientific background in senescence and is based at the SENS Research Foundation, which provides strong support with a track record of successful spin-outs (e.g. Underdog Pharma 1). The removal of senescence cells is an attractive therapeutic approach to combat aging and promote longevity. Data from Dr. Sharma’s team and others showing NK cell cytotoxicity towards senescent cells provides proof-of-concept that using CAR-NK cells is a feasible strategy to eliminate senescent cells. The team’s identification of senescence-specific cell surface markers in vitro is extremely promising and if these markers are also expressed in senescent cells in vivo, this has the potential to be an effective senolytic therapy.

VitaStem-Hematopoietic Stem Cell Rejuvenation

Unlocking longevity through in-situ Hematopoietic Stem Cell Rejuvenation using combined modulation of aging-disrupted pathways identified by publicly available and proprietary single-cell datasets from young and old human populations. Stem-cell exhaustion is a key hallmark of aging, contributing to impaired tissue repair, immune dysfunction, and systemic frailty. In this project, we took a novel approach to this challenge—rather than replacing aged blood-forming stem cells (HSCs) through transplantation, the project seeks to rejuvenate the body’s own stem cells in situ. We have analysed nearly 850,000 single-cell transcriptomes from healthy donors aged 23 to 91 from publically available and proprietary datasets, generating a high-resolution atlas of hematopoietic aging. The data reveal consistent age-related molecular signatures: younger HSCs show elevated expression of DNA repair and mitochondrial genes, while older cells exhibit ferroptosis drivers, inflammatory signaling (notably TNF and IL-17), and upregulation of CCR9 and long non-coding RNAs. These findings were confirmed in both circulating and bone marrow-derived HSCs, reinforcing their potential as biomarkers and intervention targets. In conclusion, we have identified a list of target genes, which can be used as a intervention for hematopoietic stem cell rejuvenation studies. The key insight is that we are targeting multiple aging mechanisms simultaneously - transcriptional stress responses, epigenetic regulation, and protein homeostasis. Classic damage repair thinking applied to the molecular level. This multi-pronged approach could achieve the robust rejuvenation that single interventions miss.

FOXO3

This project will design a new RNA therapeutic that nudges the longevity-linked FOXO3 gene into its health-promoting form to halt the tissue breakdown behind degenerative disc disease—opening a precise, scalable route to drugs that extend healthspan.

Matrix Bio - Long-lived Species Inspired Longevity Biotech

Naked mole rats (NMR) are long-lived rodents with a lifespan of up to 40 years, compared to normal rats which live about three years. Unlike other rodents, NMR are found to be cancer resistant. Previous research by the Gorbunova lab has demonstrated cancer resistance in NMR is modulated by the abundance of high molecular weight hyaluronic acid (HMW-HA) in tissues. Additional research has demonstrated that transgenic mice expressing naked mole rat hyaluronan synthase gene (NHAS2) have fewer tumours, improved health, and live 10% longer than mice without the transgene. Matrix Bio, in this project funded by VitaDAO, aims to increase HA in human patients and translate these findings into the clinic, this project will screen and develop small molecule inhibitors of hyaluronidases, the enzymes that break down hyaluronic acid. These compounds can be used for cancer treatment and are expected to increase human healthspan and lifespan.

Mutation-Specific Codon Suppression for Aging and Longevity

Artan Bio has proposed a novel approach to address genetic and age-related diseases caused by nonsense mutations. These mutations lead to premature protein translation stops, resulting in incomplete and nonfunctional proteins. The solution involves an engineered suppressor system that specifically recognizes these codons and restores normal protein translation.

The Longevity Molecule

The study, consisting of over 1.4 billion prescriptions, found that a number of prescription drugs were highly associated with longer life- and health-span in long-live populations. Here, we present a unique investment opportunity. We seek to validate these observations through a series of carefully conducted wet lab experiments. If successful, this work could result in the repurposing of several FDA-approved therapeutics for the purpose of extending human lifespan, at a lower cost and over faster timelines than conceivably possible with de novo drug discovery. This unique investment opportunity allows savvy longevity investors the chance to own a share of the potential intellectual property generated from these studies, and in turn, a potential share in the future of life extension. Aims, Hypothesis & Results The global elderly population is projected to substantially increase throughout the 21st century. By the year 2100 a fifth of the total world population will be aged 65 or older, posing a serious socioeconomic challenge to societies world-wide. Interventions that ensure healthy aging are therefore of critical importance. Timeline The Scheibye-Knudsen Lab will test the identified drugs' ability to attenuate features of aging in a controlled laboratory setting. Here, the molecules will be tested in human cells and in the animal model drosophila melanogaster (fruit flies). Fruit flies are used extensively in biomedical research and particular aging research as they have a short lifespan of about 60 days. Additionally, the drugs will be tested in human cells to rapidly understand how the molecules affect human cellular aging.