Advancing technology for the long-term benefit of life.
2023 Foresight Longevity Frontiers Workshop
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Thank you to our sponsors!
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Links of relevance
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Apart from scientific progress, what are the biggest headaches holding back progress?
→ Who would need to do what, including people in this room?
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Day 2 Project proposals
(+ platforms for clinical trials, + to find the senescome?)
(e.g. via at home diagnostics, new biosensors, wearables)
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Project title
Promote the use of biomarkers of aging in clinical trials
14 people, Tina Woods, Marielle Van Kooten, Karl Pfleger, Jim, Greg Fahy, Steve Horvath
What are you trying to do? Explain it in as few words as possible with zero jargon.
Goal 1. Promote the use of biomarkers of aging to inform that study of baseline characteristics of participants in future and past clinical trial
Goal 2: Lay the groundwork for future surrogate endpoints of anti aging interventions.
How is it done today? What are the limitations of the current system?
What is new in your approach and why do you think it will be successful?
What does success look like? Who cares? What is a concrete beneficial capability that could be enabled by this technology?
Are any risks associated with this project? What do you do to mitigate them? Is it possible to differentially advance safety-enhancing aspects of the technology first?
How much will it cost?
Each methylation array costs less than 200 dollars.
How long will it take?
6 months.
What are the mid-term and final exams to check for completeness?
Follow up zoom meetings.
What are your next steps if awarded a $1k, $2k, or $3k development grant?
$3k: engage with the ITP mouse consortium to send mouse samples.
Working group prompts for project proposals
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Morpheia- Continuous Biotracking Implantables
Making continuous, high-resolution and consistent Biotracking accessible
Participants interested in exploring the project (+potential role, e.g. driver, advisor, etc)
Vlad Bouchouev - driver
Timothy Vu - advisor
Nic Palmarini - adoption
mike Sinn - Data Aggregation and Analysis
Bennett Alexander - lab automation / MS student
Lucy Fauth - Engineering Lead
What are you trying to do? Explain it in as few words as possible with zero jargon.
How is it done today? What are the limitations of the current system?
What is new in your approach and why do you think it will be successful?
What does success look like? Who cares? What is a concrete beneficial capability that could be enabled by this technology?
Are any risks associated with this project? What do you do to mitigate them? Is it possible to differentially advance safety-enhancing aspects of the technology first?
How much will it cost?
-implant + subscription revenue model
How long will it take?
-15 minutes to install and set up by a medical professional with local anesthetic
What are the mid-term and final exams to check for completeness?
-hardware reliability
-upgradavility
What are your next steps if awarded a $1k, $2k, or $3k development grant?
-seed investment
-talent exploration
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Morpheia- Continuous Biotracking Implantables
Tracking Beyond Wearables
Market Entry → Expansion
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Morpheia- Continuous Biotracking Implantables
Technical Risks
Existential Hopes
Short term:
Increase Quality Adjusted Life Years (QALY) for preventable disease
Long Term:
Paradigm shift in personalized diagnostic healthcare
Who We Are
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Project title: Form Consortium for Stage 0 cancer intervention with enhanced cancer surveillance and new treatment modalities.
Participants interested in exploring the project (+potential role, e.g. driver, advisor, etc)
What are you trying to do? Explain it in as few words as possible with zero jargon.
How is it done today? What are the limitations of the current system?
What is new in your approach and why do you think it will be successful?
What does success look like? Who cares? What is a concrete beneficial capability that could be enabled by this technology?
Are any risks associated with this project? What do you do to mitigate them? Is it possible to differentially advance safety-enhancing aspects of the technology first?
How much will it cost?
How long will it take?
What are the mid-term and final exams to check for completeness?
What are your next steps if awarded a $1k, $2k, or $3k development grant?
Working group prompts for project proposals
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Project title
AgeNet: The Longevity AI Atlas
Participants interested in exploring the project (+potential role, e.g. driver, advisor, etc)
Carlos Galicia, JJ Ben-Joseph, Ravi Pandya, Johnny Adams, Guido Putignano, Jordan Baechle
What are you trying to do? Explain it in as few words as possible with zero jargon.
Create a dataset called the Single Cell Longevity Atlas Dataset from the Broad Institute raw data and other sources.
Then create a reference diffusion model from this dataset which maps attributes of the cell (cell type, perturbation, age, …) to cell state (gene expression vector, or cell images).
Create a service endpoint for the so people can try the model out in the cloud (perhaps on HuggingFace hub).
How is it done today? What are the limitations of the current system?
A lot of existing work is fragmented, e.g. imaging analysis to determine the ageing phenotype of cells. It mostly focuses on one particular type of data. Datasets are not holistic. They focus on one particular type of data, without the possibility of comparing multiple sources.
However, we should still do a review of prior work to ensure we are building on top of existing work rather than duplicating effort.
What is new in your approach and why do you think it will be successful?
It is a specific and well-specified set of executable tasks using the latest well known approaches in artificial intelligence.
What does success look like? Who cares? What is a concrete beneficial capability that could be enabled by this technology?
The project would produce a public dataset and reference model that would be broadly used by researchers in the field.
Short term metrics would be number of downloads and the result of survey on usage.
Long term metrics would be citations in publications that use the model to enable their research.
Are any risks associated with this project? What do you do to mitigate them? Is it possible to differentially advance safety-enhancing aspects of the technology first?
The risks seem lower than other general datasets - it is oriented towards health and longevity, and would be hard to use for harm.
How much will it cost?
$100,000
How long will it take?
Creating the dataset: 2 months�Training a reference model: 1 month
What are the mid-term and final exams to check for completeness?
Mid-term: How does the model approach work on a smaller synthetic dataset where ground truth is known
Final exam: To the validate the model on a completely new dataset that matches the training data, and a survey/feedback on usability by the average scientist.
What are your next steps if awarded a $1k, $2k, or $3k development grant?
Making a proper grant application or funding proposal, some better documentation besides this one slide which can be used to solicit funding from government or philanthropic sources.
The funds will largely be used to hire a technical writer to help polish the proposal.
Working group prompts for project proposals
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Project title: LongevityAction.org
Participants interested in exploring the project (+potential role, e.g. driver, advisor, etc)
Driver: Mark Hamalainen,
Advisors: Christin Glorioso, Aaron King, Aaron Mayer, Nathan Cheng, Anastasia Egorova, Cat Nguyen
What are you trying to do? Explain it in as few words as possible with zero jargon.
Give every person interested in longevity specific options to get involved. Make longevity progress tangible and actionable.
Many of us are frequently contacted by people who want to help, but we often don’t have a good answer - provide a resource we can all point people to.
How is it done today? What are the limitations of the current system?
Many of us are contacted by people who want to get involved - but we often don’t have a good answer for them.
What is new in your approach and why do you think it will be successful?
Most orgs and companies are internally focused Point people to all the orgs/companies/groups/opportunities.
What does success look like? Who cares? What is a concrete beneficial capability that could be enabled by this technology?
High percentage of visitors end up taking one of the actions (and we’ll measure it)
Are any risks associated with this project? What do you do to mitigate them? Is it possible to differentially advance safety-enhancing aspects of the technology first?
No
How much will it cost?
$3000
How long will it take? 2 Months
What are the mid-term and final exams to check for completeness?
Mid:
Final:
What are your next steps if awarded a $1k, $2k, or $3k development grant?
Working group prompts for project proposals
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Project title: Nonstop Neurons: HOW TO ADDRESS BRAIN AGING
Participants interested in exploring the project (+potential role, e.g. driver, advisor, etc)
Tanya; Christin;; Adrian; Larry; Virea; Reason; Joe; Sonia, Lynne, (Lou, Cosmo)
What are you trying to do? Explain it in as few words as possible with zero jargon.
Can we consolidate existing databases - they are currently very fragmented.
Can we promote faster development towards therapies to reverse brain aging by integrating the existing data from an aging-bio perspective?
more concretely:
one possible project: test reduced inflammation in the brain: e.g. CSF1R inhibitors
How is it done today? What are the limitations of the current system?
Exercise and diet – it doesn’t work very well, and not well distributed
What is new in your approach and why do you think it will be successful?
What does success look like? Who cares? What is a concrete beneficial capability that could be enabled by this technology?
a cure for neurodegeneration. everyone can think well throughout their lifecourse
everyone should care!
concrete beneficial capacity: standard measures of cognitive function
Are any risks associated with this project? What do you do to mitigate them? Is it possible to differentially advance safety-enhancing aspects of the technology first?
Risk: No one works on it.
How much will it cost?
Low hanging fruit projects, such as running clinical trials of CSF1R inhibitors (e.g. Pexidartinib / PLX33970 to clear microglia, could be conducted comparatively cheaply.
Reforming the status of research will be a project of decades and billions in funding.
clincal trial: 30 pts, existing approved drug, $30k/pt → $1m
How long will it take?
Small set of clinical trials: 2-3 years.
Reforming the research community: 20+ years
What are the mid-term and final exams to check for completeness?
have we curated a set of data that is sufficiently internally coherent?
What are your next steps if awarded a $1k, $2k, or $3k development grant?
Lobby?
Can João Pedro de Magalhães (JPM) add something to his database universe? are they approachable and usable enough?
ADRC is the largest federal project, but their tech is behind the curve
a more CZI-like approach?
spatial transcriptomics, etc. – project doesn’t exist
$3k: conduct a survey of the 100 top neurodegeneration researchers – what do they need to see from aging perspective? would involve travel, scientific astuteness, openness to breadth of field (pathologists, basic scientists, clinicians, funding bodies? NIA?)
Working group prompts for project proposals
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Project title: Constructive Pessimism
Participants interested in exploring the project (+potential role, e.g. driver, advisor, etc)
What are you trying to do? Explain it in as few words as possible with zero jargon.
Provide visibility to negative results in the science of longevity. Voice reservations about key scientific directions. Support critical thinking and save the longevity community time, energy and money.
How is it done today? What are the limitations of the current system?
Largely not done today. The current system rewards positive results. Negative results and reservations are published in low impact journals and reduced to backroom gossip. Current landscape is very susceptible to information cascades.
If a reputable scientist is asked for criticisms of a given domain, they can answer with sources but if they publish those answers in a comprehensive overview, it will hurt their career.
What is new in your approach and why do you think it will be successful?
What does success look like? Who cares? What is a concrete beneficial capability that could be enabled by this technology?
Are any risks associated with this project? What do you do to mitigate them? Is it possible to differentially advance safety-enhancing aspects of the technology first?
How much will it cost?
How long will it take?
What are the mid-term and final exams to check for completeness?
What are your next steps if awarded a $1k, $2k, or $3k development grant?
Working group prompts for project proposals
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Project title: Partial Reprogramming Bounceback and Master Regulators of Aging
Participants interested in exploring the project (+potential role, e.g. driver, advisor, etc)
Yuri Deigin, Alex Pickett, Cosmo Mielke, Alex K. Chen
What are you trying to do? Explain it in as few words as possible with zero jargon.
Understand how to prioritize partial reprogramming approaches within the broad context of anti-aging therapeutics. There are some signs that partial reprogramming must be repeated through the lifespan of an animal in order to retain therapeutic benefits. Since partial reprogramming ablates known epigenetic markers of aging, it is possible and perhaps even likely that any bounceback effect to the animals biological age is mediated by extracellular signals, such as factors circulating in serum, neuronal signalling to tissue, or even through distributed representations of age located extracellularly, such as in the ECM.
If there is a bounceback effect, it is important to understand the relative degree of bounceback; the stronger the degree of bounceback (ie, the degree ti which the tissue returns to its approximate chronological age), the greater likelihood that it is driven by a central regulatory system of aging rather than purely local or stochastic effects. If such a master regulator does exist, efforts to drug it may be particularly fruitful and worth further consideration by the longevity community.
How is it done today? What are the limitations of the current system?
Partial reprogramming is usually studied with the intent of driving rejuvenation and extending lifespan. There is a certain element of dose-finding, whereby reprogramming inducers are repeatedly administered until the desired effects are achieved. There is some evidence that repeat dosing is required for long-term rejuvenative effects. (Browder et al 2022). To our knowledge, there is no observed in vitro bounceback effect. This suggests that if a bounceback effect is observed in vivo, that it is driven by an explicit signal.
What is new in your approach and why do you think it will be successful?
We suggest deliberate study of ‘null’ or ‘negative’ experimental results in partial reprogramming, ie when partial reprogramming fails to achieve a long-term rejuvenative effects despite short-term confirmation of successful reprogramming. In particular, we would like to see whether biological age bounces back in the weeks and months after reprogramming.
If there is no bounceback effect, then we would remain confident that partial reprogramming should be one of the core efforts of the longevity community. If there is a substantial bounce back effect, it is clearly in the longevity community’s interest to understand how that effect is mediated.
What does success look like? Who cares? What is a concrete beneficial capability that could be enabled by this technology?
Success would be a definitive answer to those questions, which would be of interest to anyone exploring therapeutics in the longevity landscape. If a bounceback effect is real and durable, investigation of its biological basis could lead to new therapeutic targets. Further experimental directions include understanding what genetic changes are broadly selected for within animals of different lifespan within closely related genuses, understanding how nutrient sensing feeds into aging and life history, and exploring neural or hypothalamic correlates of the clock.
Are any risks associated with this project? What do you do to mitigate them? Is it possible to differentially advance safety-enhancing aspects of the technology first?
Experimental failure. That said, if a bounceback effect is not observed, it should lead to increased confidence in partial reprogramming approaches.
If a bounceback effect is observed, it would enable a program of research to identify central regulators of aging.
How much will it cost?
The minimal animal experiments are several hundred thousand to a million dollars. Further exploitation of results would require both in vivo research and bioinformatic studies.
How long will it take?
Approximately a year to assess the preliminary question depending on availability of animals an the duration of the in life portion of the experiment.
What are the mid-term and final exams to check for completeness?
Getting input from other partial reprogramming researchers to see whether there already exist definitive data that can address the core question.
Getting input from other researchers that these experiments are of interest and justify the expenditure.
What are your next steps if awarded a $1k, $2k, or $3k development grant?
$2k: Writing a detailed experimental protocol and lab setting.
Working group prompts for project proposals
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Closing session:
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Longevity events of interest
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Restaurant | Address | Distance walk (mins) |
28 Fremont St, San Francisco, CA 94105 | 2 | |
342 Howard St, San Francisco, CA 94105 | 3 | |
123 2nd St, San Francisco, CA 94105 | 5 | |
149 2nd St, San Francisco, CA 94105 | 6 | |
Tokyo Hot Chicken San Francisco | 101 California St, San Francisco, CA 94111 | 6 |
Per Diem - Financial District | 43 Sutter St, San Francisco, CA 94104 | 7 |
110 Natoma St, San Francisco, CA 94105 | 7 | |
360 Pine St, San Francisco, CA 94104 | 8 | |
374 Bush St, San Francisco, CA 94104 | 9 | |
453 Bush St, San Francisco, CA 94108 | 10 |
Dinner recommendations for Monday evening’s self-organized dinners
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