The Optispan Podcast with Matt Kaeberlein

No single discipline or approach holds the key to making big strides in the longevity field. Human aging is incredibly complex, and we're going to need multiple shots on goal in our pursuit of human life- and healthspan extension. At the Optispan Podcast, we're always excited to learn about the various angles researchers and founders are taking to advance our understanding of longevity and get impactful therapeutics that will transform human health into the clinic.

In this episode, Ora Biomedical CEO and cofounder Mitchell Lee gives us the lowdown on doing high-throughput drug discovery using a combination of worms, robotics, AI, and the general public. Matt and Mitchell talk about the company's ambitious goal to create the world's largest and most rigorous database of longevity interventions, and how a new robotics and AI data analysis platform is helping the company get there. They discuss the state of drug discovery in the longevity field, whether we can really believe any data we get from worms, the intervention that killed all their worms in one day, and more.

Prior to cofounding Ora Biomedical, Mitchell spent his career focused on scientific research and mentorship, mentoring nearly 50 trainee researchers of all levels during his graduate and postdoctoral research periods. He was the founding Chair of the American Aging Association (AGE) trainee chapter, which offers early-career financial, career development, and networking benefits, and has served on the AGE Executive Committee and Board of Directors. Mitchell received a B.S. in biology, a B.A. in philosophy, and an M.S. in biology from Western Washington University. He completed his PhD in Experimental Pathology at the University of Washington School of Medicine, during which time he received a Howard Hughes Medical Institute (HHMI) Gilliam Fellowship for Advanced Study.

Matt is a cofounder and Chair of the Board of Directors of Ora Biomedical.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

WormBot: A high-throughput system for studying aging in C. elegans

This animation explains the mechanics of the WormBot-AI platform in a clear and accessible way.

The million-molecule challenge: a moonshot project to rapidly advance longevity intervention discovery

In this article, Mitchell, Matt, and their colleagues propose the Million Molecule Challenge, a plan to screen one million interventions in C. elegans, a nematode worm, for their effects on longevity. They describe their reasoning for using C. elegans as a model organism as well as the WormBot-AI robotics platform they have developed to facilitate this high-throughput screening. They also present a proof-of-principle screen of 1,266 compounds that they completed in one month using their WormBot-AI technology.

The Million Molecule Challenge for Life Extension - Matt Kaeberlein at Longevity Summit Dublin

Matt spoke at the Longevity Summit Dublin 2023, a gathering of researchers, founders, and other leaders in the longevity field, about moving longevity science into clinical practice, how close we are to "solving aging", and what we need to make an impact in the field. About halfway through the talk, he talks about the Million Molecule Challenge: why C. elegans are a reasonable model organism with which to study aging, how much of the intervention space we have explored, and why we need a Million Molecule Challenge at all. He also presents a time-lapse video of the WormBot-AI technology, an AI and robotics platform for studying the effect of interventions on C. elegans, in action.

Using C. elegans for aging research

This short article reviews the history of using C. elegans in geroscience research. It also discusses several reasons that C. elegans is a suitable model organism for studying aging, such as cost, short lifespans, and evolutionary conserved lifespan pathways; as well as the disadvantages of using C. elegans in geroscience research, including a lack of complexity in the organism and limits to biochemistry due to the worms' small size.

Rise of the WormBots: it’s time to scale up longevity R&D

Longevity.technology profiled Ora Biomedical and interviewed Mitchell about the company's development strategy, scale of operations, and plans for the future. Mitchell describes his aim to get from longevity biotech 1.0 to longevity biotech 2.0: "discovering the next generation, most efficacious interventions".

We talk a lot about the science of longevity and healthspan on the Optispan podcast—how DEXA scans work, what an optimal rapamycin dose might look like, how the intersection of optogenetics and mitochondria are helping us understand biological aging, what supplements one might consider taking and why.

But the longevity field runs on way more than just science. It takes a village—a community of researchers, engineers, entrepreneurs, investors, regulators, and beyond who believe in the value of tackling the biology of aging as a crucial strategy for extending healthy lifespan—to create tangible results that benefit as many people as possible. At Optispan, we're eager to support and interact with the many levers that keep this machine going. One of these is the Alliance for Longevity Initiatives (A4LI), a nonprofit organization focused on catalyzing social and political action that will benefit the longevity field.

In this episode, Matt chats with A4LI founder, president, and CEO Dylan Livingston about forming a bipartisan longevity science caucus, redirecting funding towards geroscience research, and engaging with policymakers to help them understand the importance of transitioning towards a proactive healthcare model. Dylan, who founded A4LI in 2021, served as a field organizer for President Joe Biden's 2020 presidential campaign. He also worked as a community organizer for Organizing Corps 2020, where he registered hundreds of Democratic voters in Pennsylvania for the 2020 presidential compaign. Dylan graduated from Haverford College with a B.S. in physics and a minor in economics.

Matt joined the A4LI Board of Directors in 2024.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Longevity Gets Political at an Unprecedented DC Event

Lifespan.io, a nonprofit organization that aims to help accelerate discovery in the aging field through journalism, crowdfunding, and community building, profiled a two-day congressional briefing on longevity science held at Washington, D.C.'s Mayflower Hotel in April 2024. The event included presentations from Matt and other longevity biotech startup founders such as Kristen Fortney (BioAge) and Joe Betts-Lacroix (Retro Biosciences). Attendees also heard from former Speaker of the House Newt Gingrich, Republican Congressman Gus Bilirakis, and Democratic Congressman Paul Tonko.

A Policymaker’s Guide the Longevity Therapeutics Industry

This guide serves as a primer on the ever-evolving longevity space for policymakers. It describes the dominance of aging as a risk factor in chronic diseases such as cancer and diabetes, the thesis behind the geroscience approach, and recent academic and industry initiatives in longevity medicine. It also addresses several arguments for and against tackling age-related diseases and lifespan—think overpopulation, economic disparity, and the "unnaturalness" of longer lifespans—and ends with concrete steps that policymakers can take to help advance the field.

The Advanced Approval Pathway for Longevity Medicines

This document proposes a special approval track for longevity medicines to accelerate the development process for drugs that tackle the biological aging process. It includes standards for designating a therapeutic as a longevity medicine and solutions for overcoming status quo barriers such as a priority review voucher system and patent term extensions.

How can ARPA-H be a transformative agency to advance the development of biotechnology that targets human aging?

The Advanced Research Projects Agency for Health (ARPA-H) is a National Institutes of Health (NIH) entity that aims to accelerate the development of transformative solutions to our greatest health challenges. The agency provides funding to support high-impact, high-risk, high-reward research in the private and public sectors under the leadership of a Program Manager who champions a core idea and uses their subject matter expertise to see the idea to fruition. This post provides several examples of how ARPA-H might support the longevity field.

Make Your Voice Heard: Contact Your Representative on Behalf of Longevity Science

A4LI has prepared a letter template for you to use in the event that you want to request that your congressperson provides support to longevity initiatives. You are welcome to customize the letter as you see fit, and may email A4LI at info@a4li.org if you need any assistance, such as contact information for your congressional office, to send the letter.

Optogenetics is a cutting-edge field at the intersection of optics and genetics. This technique introduces microbial opsins, light-sensitive proteins naturally found in certain microorganisms such as algae and bacteria, into specific organelles, cells, or tissues to make them sensitive to light and thus precisely manipulable. Optogenetics has served as a powerful tool in neuroscience research, enabling scientists to dissect complex neural circuits and understand how they give rise to behavior, cognition, and disease; and is expanding its reach to other fields such as endocrinology, vision restoration, and muscle physiology.

In this episode, researcher Brandon Berry chats with Matt about the development and application of optogenetic tools to manipulate mitochondrial function in cells. He shares his experiences with engineering optogenetic proteins for mitochondrial targeting, the challenges involved in controlling mitochondrial charge, and the potential of optogenetics to manipulate mitochondrial membrane potential. He also discusses the complexities of mitochondrial dysfunction, the relationship between mitochondrial dysfunction and aging, and the role of mitochondrial membrane potential in longevity interventions, including caloric restriction.

Brandon, who is currently working on a stealth project, was a former postdoctoral research associate in Matt's lab at the University of Washington, where he did a lot of his work on developing tools for mitochondrial control. He received a PhD in Physiology from the University of Rochester.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Why Are Cells Powered by Proton Gradients?

This article discusses biochemist Peter Mitchell's model of proton gradients' role in cellular respiration. Proton gradients power the synthesis of adenosine triphosphate (ATP, an energy-providing nucleotide), providing a crucial mechanism for cellular metabolism. The article also explores how reliance on proton gradients might have constrained the evolution of complexity until the advent of eukaryotic cells, which harnessed mitochondria to control these gradients and may have facilitated the leap to multicellular life forms. Mitchell's proposition, though initially controversial, ultimately earned him a Nobel Prize and reshaped our understanding of cellular energy production.

Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins

This article describes an optogenetic approach that enables precise control of mitochondrial membrane potential through light-dependent activation of channelrhodopsins—light-sensitive proteins—targeted to the inner mitochondrial membrane. The method offers insights into cellular processes without the drawbacks of conventional pharmacological interventions.

Optogenetic control of mitochondrial protonmotive force to impact cellular stress resistance

Brandon is the lead author on this paper describing the engineering of an optogenetic technique for increasing the proton gradient, or protonmotive force, in worm mitochondria. "Charging up" mitochondria in this way has several beneficial effects for mitochondria, including increased resistance to toxins, better ATP synthesis, and hypoxia resistance.

Optogenetic rejuvenation of mitochondrial membrane potential extends C. elegans lifespan

In the podcast, Brandon discusses lifespan experiments he conducted to assess the impact of optogenetic mitochondrial manipulation on longevity. This study presents his finding that optogenetically controlling mitochondria slows aging and improves measures of healthspan in worms.

Extending lifespan by rejuvenating mitochondrial membrane potential - Dr Brandon Berry

Brandon chats with Eleanor Sheekey of The Sheekey Science Show about his mtON tool and its effects on worm lifespan. He provides an introduction to mitochondria ("the best organelles ever") and its role in cells, discusses the potential role of mitochondria in aging and age-related biological processes such as cellular senescence, offers some advice for aspiring academics, and more.

Senescent cells, cells that cease to divide and proliferate while remaining metabolically active, are a complex and intriguing aspect of biological aging. They serve as both a protective mechanism against cancer, preventing damaged cells from uncontrollable replication, as well as a contributor to tissue dysfunction and age-related pathologies such as cardiovascular disease, neurodegenerative disorders, and diabetes. The precise mechanisms that underlie senescence and its contributions to the aging process remain areas of ongoing investigation and debate.

In this episode, Matt chats with Sapere Bio co-founder and CEO Natalia Mitin about measuring cellular senescence, using those measurements in the clinic, and the complex and heterogeneous role of cellular senescence in aging and disease. They also discuss Natalia's personal experiences using rapamycin off-label to improve energy levels and immune function, the importance of monitoring biomarkers when using off-label medications, and Natalia's thoughts on "rapamycin for all".

Prior to co-founding Sapere Bio, Natalia served as an assistant professor at the University of North Carolina at Chapel Hill's Department of Pharmacology. She spent over two decades developing assays for use in cancer research. She holds a B.S. in chemical engineering from the Mendeleev Institute for Chemical Technology and a PhD in biochemistry and molecular biology from Bowling Green State University.

Optispan uses the SapereX test in its healthspan optimization program.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders

This seminal paper demonstrated a potential causal link between cellular senescence and various aging phenotypes. Removing senescent cells exhibiting the kinase inhibitor and senescence biomarker p16 delayed the onset of age-related phenotypes in mouse skeletal muscle, adipose, and eye tissues.

Naturally occurring p16 Ink4a-positive cells shorten healthy lifespan

This paper, which shares several authors with the previous one, showed that clearing senescent cells impeded tumor and cataract formation as well as age-related deterioration of organs and tissues including kidney, heart, and fat in mice. It also extended lifespan in mice from two different genetic backgrounds that were eating different diets.

Senolytics improve physical function and increase lifespan in old age

If you want to prematurely age a mouse, give it a senescent cell transplant. Transplanting senescent cells into young mice led to physical dysfunction, the spread of cellular senescence to host tissues, and reduced survival in mice. Selective elimination of senescent cells via senolytic therapy alleviated these negative effects and increased survival after treatment by 36%.

Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging

This study found an association between the kinase inhibitor and senescence biomarker p16 and human chronological age. It also found a more rapid increase in p16 expression with older age in those who smoked compared with those who didn't smoke, a finding consistent with other evidence for tobacco smoke's age-accelerating effects; as well as a relationship between the expression of p16 and interleukin-6 (IL-6), a cytokine that plays an important role in cell signalling and can serve as a biomarker of inflammation.

A quantitative model for age-dependent expression of the p16INK4a tumor suppressor

This paper presents results from computational modeling of p16+ cellular senescence dynamics in healthy people. The model revealed how the p16 accumulation rate changes with chronological age and lifestyle factors such as smoking and exercise habits.

University of Arizona Assistant Professor of Molecular and Cellular Biology George Sutphin runs a lab that investigates genetic determinants of longevity, the effects of kynurenine-based interventions on lifespan, and environmental regulators of the aging process. George, who was an aerospace engineer before he discovered the promise of geroscience, completed his PhD at the University of Washington and worked as a postdoctoral associate at the Jackson Laboratory prior to his current faculty position. He currently serves as Chairperson of the American Aging Association.

We sat down with George to talk about his research, including the effects of caffeine on lifespan and, more recently, his discovery of a new metabolite with the ability to greatly extend lifespan when given late in life. We also discuss George's thoughts on biological age clocks, his own healthspan optimization protocol, and much more.

The probiotic George mentions taking in this podcast episode is Garden of Life Probiotics Ultimate Care.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Caffeine extends life span, improves healthspan, and delays age-associated pathology in Caenorhabditis elegans

This paper began as a side project during George’s PhD work at the University of Washington. It showed that caffeine extended life- and healthspan in nematode worms, and also had positive effects on pathologies such as paralysis in a worm model of polyglutamine disease. The paper attracted a lot of interest, perhaps because it seemed to justify people’s coffee-drinking habits. No conclusive evidence about caffeine’s effects on human lifespan currently exists.

Lifespan extension in Caenorhabditis elegans by complete removal of food

What is the optimal amount of food to give worms so that they’ll live longer? According to this study, which also came out of George’s PhD at the University of Washington, the answer is no food at all. This paper found that completely taking away worms’ food in adulthood increased lifespan by up to 50%. While a starvation protocol like this one is unlikely to work in humans, these findings add an interesting set of data points to evolving research into how diet affects longevity in humans.

Dietary restriction by bacterial deprivation increases life span in wild-derived nematodes

This study was a follow up to the previous paper and investigates the effects of dietary restriction on the lifespan of wild worm populations collected from various locations worldwide. The results indicate that bacterial food deprivation extends lifespan across multiple wild C. elegans (a worm species) populations. Additionally, the longevity-enhancing effects of bacterial food deprivation are conserved in a related worm species, C. remanei. The study highlights the potential impact of genetic and environmental factors on worm lifespan variation and suggests that food-deprivation-induced lifespan extension may be a characteristic of wild-derived nematode populations.

Caenorhabditis elegans orthologs of human genes differentially expressed with age are enriched for determinants of longevity

This paper came out of George’s time at the Jackson Laboratory. The researchers conducted an RNA interference (RNAi) longevity screen on 82 genes in C. Elegans, chosen based on their orthology to human genes that show age-related changes in expression. Their results revealed a significant enrichment in genes where knockdown increased lifespan compared to previously published longevity screens, with 46 genes being newly identified as impacting lifespan. Knockdown of these genes, which included genes that encoded the enzyme kynureninase, a tetraspanin, and a voltage-gated calcium channel subunit, increased healthspan with no effects on reproduction. The kynureninase gene knockdown specifically delayed pathology in worm models of Alzheimer's and Huntington's diseases.

The Emerging Role of 3-Hydroxyanthranilic Acid on C. elegans Aging Immune Function

3-hydroxyanthranilic acid (3-HAA) is a metabolite within the kynurenine pathway, a metabolic pathway involved in the breakdown of the amino acid tryptophan. The kynurenine pathway plays a crucial role in various physiological processes, including immune response regulation, neurotransmitter synthesis, and inflammation modulation. This paper showed that the 3HAA appeared to slow age-associated immune function decline in addition to helping mice fend off pathogenic challenges. 3HAA is not sufficiently well-understood to be a candidate for supplementation in humans.

Optispan CEO Matt Kaeberlein chats with Prime Health Associates Physician Kevin White about making the transition from research to building a company, moving towards preventative medicine in the 21st century, incorporating new discoveries into medical practice, and more.

Optispan CEO Matt Kaeberlein chats with Prime Health Associates Physician Kevin White about improving bloodwork results, monitoring glucose readings, taking supplements, and more.

Matt and guest Jonathan An, Assistant Professor of Oral Health Sciences at the University of Washington School of Dentistry, discuss oral health and its relationship to aging, including published studies involving rapamycin effects on oral health. This is a 3-part episode.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Aging and Oral Health with Dr. Jonathan An!

Our guest, Assistant Professor of Oral Health Sciences and Faculty in the Healthy Aging and Longevity Institute at the University of Washington School of Dentistry Jonathan An, recently appeared on Lets Get Oral, a podcast that explores oral health from multiple angles—think the oral microbiome, taste, bad breath. In this episode, Jonathan talks about how our teeth change as we get older, the potential impact of medications on oral health, why he supports taking a more systemic approach to dental care, and more.

Oral health in geroscience: animal models and the aging oral cavity

Animal models are indispensable tools for studying the biology of aging. They provide insight into underlying mechanisms of aging, enable scientists to test interventions that promote healthy aging, and advance our understanding of age-related diseases. While animal models have their limitations, their use in research allows for controlled experimentation and the generation of valuable data that can ultimately benefit human healthspan and longevity. Jonathan and our host Matt Kaeberlein co-authored this journal article about which animal models are best suited for studying the intersection of aging and oral disease. They discuss rodents, the current premier preclinical models for geroscience research, as well as dogs and nonhuman primates such as the southern pig-tailed macaque.

Rapamycin rejuvenates oral health in aging mice

In 2020, Jonathan and Matt demonstrated that rapamycin treatment rejuvenated the aged oral cavity of older mice. The treatment reversed "clinically defining features of periodontal disease", including periodontal bone loss, periodontal inflammation, and pathogenic oral microbiome changes. This paper lends support to the idea that interventions that target mechanisms of biological aging may delay multiple age-related declines. Further work should investigate whether the rejuvenating effects of rapamycin persist after the treatment period as well as whether rapamycin improves other oral health declines that commonly occur with age, such as salivary function.

Oral health for healthy aging

This article calls for an end to the siloing of oral health from general health care. The authors note that the global prevalence of oral disease is higher than it should be, given the preventable nature of most oral diseases, and that this prevalence is likely to worsen with population aging. They make suggestions for concrete policy action and mindset shifts towards addressing the burden of oral disease care, including shifting dental care models away from curative and interventionist models and towards more preventative upstream action.

Aging and Dental Health

This is a short primer from the American Dental Association about the clinical and oral health context of older adults. By one estimate, 68 percent of adults aged 65 years and older have periodontis. The primer covers comorbid conditions; the potential impact of common medications for age-related conditions on oral health; and cognitive, physical, and sensory limitations affecting dental care and home oral care.

Matt and guest Jonathan An, Assistant Professor of Oral Health Sciences at the University of Washington School of Dentistry, discuss oral health and its relationship to aging, including published studies involving rapamycin effects on oral health. This is a 3-part episode.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Aging and Oral Health with Dr. Jonathan An!

Our guest, Assistant Professor of Oral Health Sciences and Faculty in the Healthy Aging and Longevity Institute at the University of Washington School of Dentistry Jonathan An, recently appeared on Lets Get Oral, a podcast that explores oral health from multiple angles—think the oral microbiome, taste, bad breath. In this episode, Jonathan talks about how our teeth change as we get older, the potential impact of medications on oral health, why he supports taking a more systemic approach to dental care, and more.

Oral health in geroscience: animal models and the aging oral cavity

Animal models are indispensable tools for studying the biology of aging. They provide insight into underlying mechanisms of aging, enable scientists to test interventions that promote healthy aging, and advance our understanding of age-related diseases. While animal models have their limitations, their use in research allows for controlled experimentation and the generation of valuable data that can ultimately benefit human healthspan and longevity. Jonathan and our host Matt Kaeberlein co-authored this journal article about which animal models are best suited for studying the intersection of aging and oral disease. They discuss rodents, the current premier preclinical models for geroscience research, as well as dogs and nonhuman primates such as the southern pig-tailed macaque.

Rapamycin rejuvenates oral health in aging mice

In 2020, Jonathan and Matt demonstrated that rapamycin treatment rejuvenated the aged oral cavity of older mice. The treatment reversed "clinically defining features of periodontal disease", including periodontal bone loss, periodontal inflammation, and pathogenic oral microbiome changes. This paper lends support to the idea that interventions that target mechanisms of biological aging may delay multiple age-related declines. Further work should investigate whether the rejuvenating effects of rapamycin persist after the treatment period as well as whether rapamycin improves other oral health declines that commonly occur with age, such as salivary function.

Oral health for healthy aging

This article calls for an end to the siloing of oral health from general health care. The authors note that the global prevalence of oral disease is higher than it should be, given the preventable nature of most oral diseases, and that this prevalence is likely to worsen with population aging. They make suggestions for concrete policy action and mindset shifts towards addressing the burden of oral disease care, including shifting dental care models away from curative and interventionist models and towards more preventative upstream action.

Aging and Dental Health

This is a short primer from the American Dental Association about the clinical and oral health context of older adults. By one estimate, 68 percent of adults aged 65 years and older have periodontis. The primer covers comorbid conditions; the potential impact of common medications for age-related conditions on oral health; and cognitive, physical, and sensory limitations affecting dental care and home oral care.

Matt and guest Jonathan An, Assistant Professor of Oral Health Sciences at the University of Washington School of Dentistry, discuss oral health and its relationship to aging, including published studies involving rapamycin effects on oral health. This is a 3-part episode.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Aging and Oral Health with Dr. Jonathan An!

Jonathan recently appeared on Lets Get Oral, a podcast that explores oral health from multiple angles—think the oral microbiome, taste, bad breath. In this episode, Jonathan talks about how our teeth change as we get older, the potential impact of medications on oral health, why he supports taking a more systemic approach to dental care, and more.

Oral health in geroscience: animal models and the aging oral cavity

Animal models are indispensable tools for studying the biology of aging. They provide insight into underlying mechanisms of aging, enable scientists to test interventions that promote healthy aging, and advance our understanding of age-related diseases. While animal models have their limitations, their use in research allows for controlled experimentation and the generation of valuable data that can ultimately benefit human healthspan and longevity. Jonathan and our host Matt Kaeberlein co-authored this journal article about which animal models are best suited for studying the intersection of aging and oral disease. They discuss rodents, the current premier preclinical models for geroscience research, as well as dogs and nonhuman primates such as the southern pig-tailed macaque.

Rapamycin rejuvenates oral health in aging mice

In 2020, Jonathan and Matt demonstrated that rapamycin treatment rejuvenated the aged oral cavity of older mice. The treatment reversed "clinically defining features of periodontal disease", including periodontal bone loss, periodontal inflammation, and pathogenic oral microbiome changes. This paper lends support to the idea that interventions that target mechanisms of biological aging may delay multiple age-related declines. Further work should investigate whether the rejuvenating effects of rapamycin persist after the treatment period as well as whether rapamycin improves other oral health declines that commonly occur with age, such as salivary function.

Oral health for healthy aging

This article calls for an end to the siloing of oral health from general health care. The authors note that the global prevalence of oral disease is higher than it should be, given the preventable nature of most oral diseases, and that this prevalence is likely to worsen with population aging. They make suggestions for concrete policy action and mindset shifts towards addressing the burden of oral disease care, including shifting dental care models away from curative and interventionist models and towards more preventative upstream action.

Aging and Dental Health

This is a short primer from the American Dental Association about the clinical and oral health context of older adults. By one estimate, 68 percent of adults aged 65 years and older have periodontis. The primer covers comorbid conditions; the potential impact of common medications for age-related conditions on oral health; and cognitive, physical, and sensory limitations affecting dental care and home oral care.