Introduction
Welcome back Vitalians and please join us in congratulating the Cyclarity Therapeutics (CTx) team for passing the VitaDAO token holder vote! This proposal was an assessment of an early-stage biotechnology company that is developing novel cyclodextrin drug molecules to extract toxic biomolecules that accumulate with age.
Whilst all of the humans were either at ARDD or on holiday, we took the opportunity to interview our favourite silicon friend, ChatGPT to ask its thoughts on longevity research. And talking of AI, we hope you are enjoying the new artwork peppered throughout our newsletter!
Longevity Literature Hot Picks
Preprint Corner
The second edition of The Longevist is now live! Check it out to see what our team of expert curators think are the best preprints of Q2.
We’re excited to bring you our second batch of preprints of Q3 with these August submissions. These will each be entered into the Q3 longlist to be in the running to receive a coveted place in The Longevist. They are also available to review on our reviewing platform The Longevity Decentralized Review (TLDR) for a bounty of 50 VITA per review.
As always, you can refer preprints to The Longevist and receive a bounty of 50 VITA for each one that makes the editors’ shortlist or 200 VITA if it makes the curators’ top 3.
Reversal of Biological Age in Multiple Rat Organs by Young Porcine Plasma Fraction
On standardization of controls in lifespan studies
Published Research Papers
Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice
By introducing the naked mole-rat hyaluronic acid synthase 2 gene (nmrHas2) into mice, researchers observed increased hyaluronan levels, reduced cancer incidence, extended lifespan, improved healthspan, and reduced inflammation, demonstrating the potential for HMM-HA to enhance longevity and health in other species
Universal DNA methylation age across mammalian tissues
Researchers have developed universal pan-mammalian clocks based on DNA methylation profiles, accurately estimating the age of mammalian tissues with high precision. These age estimations are linked to mortality risk in humans, somatotropic axis mutations in mice, and caloric restriction, and they highlight specific methylation changes near genes associated with development, cancer, obesity, and longevity, indicating that aging is evolutionarily conserved and connected to developmental processes across mammalian species.
Atlas of the aging mouse brain reveals white matter as vulnerable foci
Aging leads to cognitive decline with distinct molecular changes in the brain. Using mouse models, researchers identified aging patterns in glial cells. Rejuvenation treatments affected gene expression differently, suggesting regional aging may impact neurodegenerative diseases.
The impact of the cardiovascular component and somatic mutations on ageing
In a study across 15 mammals, lifespan showed a strong negative correlation with somatic mutation rate. While various traits influenced lifespan, resting heart rate stood out. Combining somatic mutation with heart rate improved lifespan predictions, indicating underlying mechanisms tied to aging.
Circadian disruptions are prevalent in Alzheimer’s disease (AD). A study showed time-restricted feeding (TRF) benefitted AD mouse models by improving memory, reducing disease markers, and adjusting disrupted gene patterns. TRF’s broad impacts suggest it could be a potential strategy to counteract AD progression.
Early-adulthood spike in protein translation drives aging via juvenile hormone/germline signaling
In Drosophila, an early adulthood increase in protein translation (PT) negatively affects aging and protein balance. Stopping this PT surge improves lifespan and reduces protein build-up. The initial PT boost disrupts protein management and accelerates aging through certain pathways. Thus, the natural post-youth PT decline might protect against age-related problems, offering a fresh angle on how PT impacts lifelong aging.
Irreversible cell cycle exit associated with senescence is mediated by constitutive MYC degradation
Cells become senescent to stop unchecked growth, but its irreversibility has been debated. This study reveals that senescence is irreversible due to MYC protein degradation. When MYC isn’t degraded, senescent cells divide; with MYC reduction, non-dividing cells become senescent.
The YAP–TEAD complex promotes senescent cell survival by lowering endoplasmic reticulum stress
Senescence stops cell growth and increases resistance to death. A study found that inhibiting the YAP–TEAD pathway with verteporfin (VPF) led to targeted death of senescent cells. This occurs by suppressing mTOR, inducing endoplasmic reticulum (ER) stress due to the demands of the senescence-associated secretory pattern (SASP).
Published Literature Reviews, Hypotheses, Perspectives and more
Challenges in developing Geroscience trials
As the geroscience field grows, refining clinical study designs becomes crucial. Challenges include selecting populations, choosing interventions, defining trial outcomes, and pinpointing key age-related biomarkers (“Gerodiagnostics”).
The evolution of selective autophagy as a mechanism of oxidative stress response
Aging reduces autophagy and increases damaging ROS. In humans, selective autophagy receptors (SARs) may have evolved to detect oxidative stress, initiating autophagy to remove damaged components and restore cellular balance, which contributes to our longer lifespan, while its loss could lead to age-related diseases.
A mammalian DNA methylation landscape
Mammals display varied lifespans, from bowhead whales at 200 years to giant Sunda rats at 6 months. Despite similar genes, gene regulation might dictate aging. Haghani et al. studied DNA methylation across mammals, identifying regions possibly affecting lifespan, shedding light on molecular lifespan determinants.
Job board
The Institute of Inflammation and Aging, with Joao Pedro, is seeking a dedicated professor with expertise in aging science and age-related diseases. This is a valuable opportunity at the University of Birmingham!
Deadline: 31 August 2023
Apollo Health Ventures are recruiting for their portfolio company (and VitaDAOs portfolio company) BE Therapeutics in New York City, looking for a Research Asscociate
McLab is announcing openings for postdoc and technician roles! Backed by new funding, they aim to delve deeper into understanding the effects of aging on breast cancer progression and therapeutic response.
Cologne Graduate School of Ageing Research
Up to 12 fully funded PhD studentships starting in October 2024
Valentin F. Cracan is seeking a postdoctoral fellow in genetically encoded sensors and tools for studying the role of redox imbalance in cancer, neurodegeneration and aging
Interested in nutrition, supplements and human trials? This Research Fellow (Nutritional Intervention) position in Andrea Maier’s lab at National University of Singapore could be for you.
Two fully funded PhD student positions in Healthy Aging Research (biochemistry, epidemiology, bioinformatics) at Charite Berlin and Humboldt University. Please apply by Sept 30th.
News and Media
The British Society for Research on Aging is pleased to announce the award of the Lord Cohen Medal to Professor Lynne Cox for her outstanding achievements and contributions to understanding the biology of aging.
GERO and FOXO Technologies embark on joint initiative on AI and epigenetic data
Anti-aging technology is here. And the Middle East is getting ready
How does aging increase risk of dehydration?
A biological clock explains why a dog year is equivalent to seven human years
Adherence to a Mediterranean lifestyle associated with lower risk of all-cause and cancer mortality
Leaders In Longevity Medicine Convene In Copenhagen
Saudi Arabia Is Dangling Billions for Research on Aging. Scientists Are Lining Up to Take It
Resources
Prizes
Rewarding the most impactful research in longevity
$250k Prize pool. 15 Winning papers. 180 Influencing papers
Conferences
British Society for Research on Aging Annual Scientific Meeting (BSRA ASM)
6–8 September, London, UK
7–9 September, LA, CA, USA
The Longevity Investors Conference (LIC) is an application-only event
27–28 September
Expo and Convention: Independent Ageing 2023
13–15 October, Aichi, Japan
7–8 November, Buck Institute for Research on Aging, Novato, CA, USA
Tweet of the Month
Shahaf Peleg:
Podcasts and Webinars
NUS Medicine’s Healthy Longevity Webinar Series
Funding Opportunities
Impetus Grants will keep applications open until September 15, 2023.
Interview with ChatGPT
Short bio
ChatGPT is developed by OpenAI and based on the GPT-4 architecture. As it likes to remind us, it is programmed to provide information based on a wide array of sources available up until 2021.
Why do you think humans are inspired to research aging?
For humans, the inspiration to study aging often comes from a deep-seated desire to improve human life, reduce suffering from age-related diseases, and extend the healthy years of human life. The field has also been inspired by observations in nature; for example, certain species of whales, tortoises, and birds exhibit remarkably slow aging and resistance to age-related diseases.
How has the longevity field changed in the last 3 decades?
The development of advanced computational tools, genome sequencing, and molecular biology techniques has allowed researchers to identify and target specific pathways related to aging.
Consequently, the attitude towards aging is now changing, as people are beginning to see it as something that can be manipulated, rather than an inevitable, untreatable process.
What do you think have been the biggest/important discoveries in the field?
Some of the most important discoveries include the identification of key genes and pathways associated with aging, such as the sirtuins, mTOR, and AMPK pathways. The discovery that the drug rapamycin, originally used to prevent organ transplant rejection, can extend the lifespan of mice has led to a surge of interest in the mTOR pathway as a target for anti-aging interventions. Also, studies on calorie restriction and its impact on lifespan have opened new avenues for research
The discovery of telomeres and the role of telomerase in cellular aging has also been pivotal. Finally, the discovery of cellular senescence and development of senolytic drugs has been a significant breakthrough.
What advice would you give to people currently working in longevity research?
Stay interdisciplinary. Aging is a complex process that affects every system in the body, so collaborations across different fields of science will be key to making significant progress. Also, consider the ethical implications of your work; extending lifespan will have profound implications for society, and it is important to consider these issues as the research progresses.
Which aspect of longevity research do you think requires more attention?
One aspect that requires more attention is the study of the social, economic, and psychological implications of increased lifespan. While much focus has been placed on the biological aspects of aging, it is equally important to understand how increased lifespan will impact society as a whole.
While a lot of focus has been on the molecular and cellular aspects of aging, the impact of the microbiome on aging is an area that requires more attention. The microbiome plays a crucial role in human health, and its composition changes with age. Understanding these changes and how they contribute to aging could open up new avenues for intervention.
Is aging a disease?
This is a controversial topic. Some researchers argue that aging should be classified as a disease to spur more funding and research into interventions. Others argue that it is a natural process and classifying it as a disease could have unintended societal implications. While there is no consensus, it is clear that aging is the biggest risk factor for many diseases, and interventions that target the aging process could have broad benefits for human health.
How would you solve aging?
Aging is a highly complex and multifaceted process. A plausible approach would be to tackle it from both a biological and a sociocultural angle:
Biologically: Focus on cellular and genetic levels. This could involve targeting senescent cells, managing telomere length, and improving proteostasis, along with employing genetic engineering techniques like CRISPR to modify or replace genes linked with aging.
Socioculturally: The intersection of technology, lifestyle, and health would have to be addressed. Integrative health systems would become a priority, where AI, human medical expertise, and regular health monitoring would ensure that people stay in the best health possible.
Do you think solving aging would facilitate humankind’s efforts to colonise the galaxy?
Yes, solving aging would significantly facilitate space exploration and colonization. With extended lifespans, the time it takes to travel between stars becomes less daunting. Humans could embark on century-long journeys to distant star systems without the fear of dying of old age.
How can AI significantly influence and advance the field of aging biology?
Data Analysis: The biology of aging generates vast amounts of data, from genetic sequencing to cellular imaging. AI can rapidly process and analyze this data, identifying patterns or anomalies that might be missed by human researchers.
Predictive Modeling: AI can develop models to predict the outcomes of various interventions on aging. For example, given the genetic and health data of an individual, an AI might predict how certain treatments could impact their aging process.
Drug Discovery: AI-driven algorithms can analyze massive compound libraries to identify potential drugs that could impact aging. They can also predict drug interactions and side effects.
Genomic Analysis: Machine learning can help identify genes associated with longevity and age-related diseases. By understanding these genes, researchers can target them for therapeutic interventions.
Simulations: AI can simulate biological processes, allowing researchers to test theories about aging in a virtual environment before conducting real-world experiments.
How can we innovate strategies that dramatically amplify human lifespan by decades or even centuries, rather than achieving mere incremental enhancements of a few years?
Radical Interventions: While current interventions might add a few years, radical approaches, like advanced gene therapy, organ replacements using lab-grown organs, or nanotechnology to repair cellular damage, might be required for substantial lifespan extensions.
Holistic Approach: Aging is multifactorial. Addressing it might require a combination of genetic, pharmacological, lifestyle, and environmental interventions.
Space and Environment: There’s emerging interest in how changing environments (e.g., space or deep-sea habitats) could impact human aging. If certain environments slow aging, they might become more appealing for habitation.
AI and Tech Integration: As discussed, AI will play a pivotal role. The seamless integration of technology and biology, such as continuous health monitoring and immediate AI-driven interventions, might be crucial.
Outro
We appreciate you sticking with our research newsletter for another month and hope the content we curate is useful! Wishing you speedy recovery after an intense conference season and see you back here next month.
This time we leave you with the first of a new article series co-written with the winners of the Longevity Prize, highlighting their proposals. Starting with the 1st prize winner Carlos Galicia and The Key to Longevity Could Be Hidden in Embryos.
Further Reading
Health Consequences of Thymus Removal in Adults
LINE-1 regulates cortical development by acting as long non-coding RNAs
