The Optispan Podcast with Matt Kaeberlein PhD
The Optispan Podcast with Matt Kaeberlein aims to bring insights from the geroscience and longevity world into the public to help people optimize their healthspan and improve their quality of life.
We believe that everyone can get closer to their own optimal healthspan. We hope you find this content valuable, subscribe to the channel, and come back often. More importantly, we hope that you apply what you learn here to recover your lost decade, and perhaps much more.
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• 12/26/24My Review of Peter Attia’s AMA: What I Agree & Disagree With
In this episode, Matt shares his thoughts on Peter Attia's AMA , exploring areas of agreement and differing perspectives on health and longevity. Topics include the significance of grip strength, biomarkers for health assessment, exercise strategies while traveling, and advancements in longevity research like Klotho and GLP-1 agonists. Matt also discusses the role of AI in healthcare and addresses concerns about direct-to-consumer biological age tests. The episode concludes with a discussion of foundational exercises and the interconnected nature of aging and health.
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!
ChatGPT With GPT-4 Outperforms Emergency Department Physicians in Diagnostic
Accuracy: Retrospective Analysis - PMC
One of the advancements that both Matt and Peter are most excited about within the geroscience field is the evolution and increasing relevance of artificial intelligence (AI) and machine learning, not just in research but also clinical care. The successful implementation of generative AI in the clinical space opens the opportunity for making clinical care more accessible and caring for underserved populations. This study demonstrates the promise of generative AI in the clinical space by retrospectively analyzing 100 adult patients admitted to the internal medicine emergency department and comparing how the ChatGPT-4 models’ diagnostic output compared to initial diagnosis made by resident physicians and evaluated both against final hospital discharge diagnosis. A point-based system was utilized to grade diagnostic accuracy, with 2 points for accurate, 1 point for partially correct, and 0 for incorrect diagnoses. Across various disease subgroups—cardiovascular, endocrine, gastrointestinal, and infectious diseases—GPT-4 consistently outperformed resident physicians, with statistical significance noted in several comparisons. This underscores the potential of AI to enhance clinical decision-making and potentially streamline clinical care in the future.
Hand grip strength as a proposed new vital sign of health: a narrative review of evidences - PMC
Matt discusses his thoughts on hand grip strength (HGS) as a robust functional marker of biological aging and emphasizes the difference between its correlation with longevity from any causative role it may play. This study conducted a narrative review to evaluate HGS as a potential “vital sign” for systemic health and age-related decline. A correlation was identified between low HGS and several diseases, including Type 2 diabetes, cardiovascular disease, stroke, chronic kidney and liver disease, certain cancers, sarcopenia, and fragility fractures. Additionally, low HGS was associated with increased hospitalization, poorer nutritional status, higher overall mortality, and reduced quality of life. One of the major limitations of HGS is that while it may be a marker of declining health and accelerate biological age, it does not inform interventional care decisions. It is unlikely that improving HGS alone is enough to mitigate the risks of adverse age-related outcomes it is strongly associated with. On the other hand, it may be a strong indicator for an individual that investing in improving functional fitness (e.g. through exercise) could significantly improve healthspan.
Matt and Peter both converge on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as one of the interventions they are most enthusiastic about in regards to improving healthy longevity. This narrative review examines the potential of GLP-1RAs to enhance healthy lifespan by addressing several age-related diseases. The review evaluates findings from clinical trials and studies to evaluate the therapeutic benefits and future applications of GLP-1 RAs. The review highlights that beyond significant benefits in managing type 2 diabetes and obesity, GLP-1 RAs have been associated with cardiovascular risk reduction and possess anti-inflammatory properties. Ongoing clinical developments suggest potential therapeutic roles for GLP-1 RAs in treating chronic kidney disease, metabolic liver diseases, and Alzheimer's disease.Their pleiotropic effects, including metabolic regulation and anti-inflammatory actions, position them as promising candidates for address multi-organ function and mitigating multi-morbidity. The review underscores the need for further research to fully elucidate the potential of GLP-1 RAs in promoting healthy aging in normative aging individuals without unmanaged disease or frailty.
https://www.nature.com/articles/s43587-023-00441-x
The peptide alpha-klothos (klotho) has been in the spotlight as a potential longevity intervention for years due to promising findings of improved lifespan in C. elegans, mice, and humans (within genetic association studies). In this study, researchers investigated the effects of klotho on cognitive function in aged nonhuman primates.The study found that a single administration of low-dose klotho enhanced memory and learning in aged nonhuman primates (sustained at least 2 weeks after administration), while the high-dose did not produce the same effect. This suggests a dose-dependent response, with low-dose klotho improving cognitive function in these primates. This positions klotho as a promising therapeutic agent for mitigating cognitive decline associated with aging in humans.
https://www.nature.com/articles/s41586-024-07701-9
In this study, researchers investigated the role of interleukin-11 (IL-11), a pro-inflammatory cytokine, in aging and age-related diseases using mouse models. They showed that both pharmacological inhibition (with an anti-IL-11 antibody) and mice genetically engineered to lack the IL-11 gene demonstrated improved lifespan (greater than 20% in males and females) and several healthspan metrics including reduced frailty, improved physical function, and a lower incidence of fibrosis and cancer compared to control mice. Mechanistic studies suggest that IL-11 may exert its effects through inhibition of mTOR, similar to rapamycin, prompting Matt to hypothesize that, while effective, this intervention may not show substantially improved longevity benefits compared to rapamycin. Further research is needed to elucidate other benefits of IL-11 on various healthspan metrics (e.g. cognition) as well as mTOR independent mechanisms through which it may be enhancing longevity.
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• 12/10/24Longevity Scientist On Ethan Klein's "Revolutionary New Drug For Dogs" Discussion (H3 Podcast)
Matt Kaeberlein & Nick Arapis discuss the potential of new drugs aimed at extending the lifespan of dogs and cats. The conversation highlights recent advancements, including Loyal’s injection-based treatment targeting the IGF-1 hormone, which may add years to a dog’s life. They also address misconceptions regarding claims about cat lifespan extensions, emphasizing the lack of scientific backing for such assertions. The episode underscores the importance of grounded scientific communication and the excitement surrounding longevity-based advancements.
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!
https://www.sciencealert.com/a-radical-new-drug-is-poised-to-extend-the-life-of-dogs
Ethan mentions Loyal’s potential lifespan-enhancing intervention (LOY-001) that could extend canine lifespan by up to five years by blocking insulin growth factor signaling. IGF-1 is thought to play a major role in the shorter lives and increased incidence of heart disease and cancer in large dogs compared to their smaller counterparts. While there is data on lifespan extension by blocking IGF-1 signaling in nematode worms, flies, and mice, there is no such data in dogs. This article discusses the conditional approval of LOY-001 which recieved FDA fast track status and may be in the market by 2026, even while evidence is still being collected within clinical trials. If Loyal's clinical trial is successful and LOY-001 extends lifespan by a minimum of one year in large dogs (at least 7 years old), it will be the first gerotherapeutic approved for use. In an observational study of 450 dogs, Loyal has already found that dogs with lower insulin levels experience reduced frailty and a higher quality of life, lending further promise to LOY-001 for enhancing healthy longevity.
https://www.nature.com/news/2006/061009/full/news061009-12.html
This short but sweet nature article describes how the IGF-1 gene was discovered to be a primary driver of dog size and how this gene may be the most manipulated gene in nature due to humans breeding practices. Little did we know that we were not only breeding dogs for size and look, but also for longevity.
Matt discusses the emerging research around the apoptosis inhibitor of macrophages (AIM) protein and claims that it can extend a cat’s life by up to thirty years. AIM is a secreted protein that can help identify and destroy dead cells and other debris in the body. Research has demonstrated that when AIM detaches itself from IgM (immunoglobulin M) antibodies, it proceeds to clean the body of waste and debris. If AIM remains attached to IgM, it no longer preserves its health-promoting functions and this leads to an increased incidence of adverse health outcomes in mouse models of kidney disease. Since kidney disease is one of the major causes of death in cat’s, it is being studied in clinical trials and offered as a longevity supplement (AIM-30) for pet cats. Based on the data in mice, Matt suggests that if successful, AIM-30 may extend the lifespan of cats by a few years at best. This paper supports the promise of targeting AIM for improving health outcomes in kidney disease patients. The authors evaluate the plasma of hundreds of patients on dialysis and find that those that show low levels of AIM dissociation before initiation of dialysis showed lower levels of inflammatory factors and cellular debris, exhibited lower risk for cardiovascular disease and had better survival than those with high levels of AIM dissociation. Further treatment of cats with kidney disease with an engineered form of AIM that does not bind to IgM prevented aggravation of renal function and inflammation and improved survival dramatically. This study supports the exaggerated claim that AIM supplementation may extend cat lifespan by up to 30 years.
Impact of feline AIM on the susceptibility of cats to renal disease | Scientific Reports
This is the original nature paper that demonstrated that the feline AIM protein binds IgM 1000x more tightly than the mouse AIM protein, contributing to increased mortality from kidney disease in cats. They support this by demonstrating that replacing mouse AIM protein with feline AIM protein in mouse models of kidney disease leads to impaired recovery from kidney injury. Further, injecting an engineered form of AIM that does not bind to IgM increased survival of mice with kidney injury by 30%.
This paper co-authored by SJ Olshansky makes the case for investing in aging research through highlighting the health and economic benefits of developing interventions that target and slow the biology of aging over the current disease-care model. The study used a model for predicting future health and economic outcomes based on three different scenarios: delaying aging, significant reduction in heart disease, and significant reduction in cancer. The model suggests that delaying aging provides the largest returns with a 2.2 year extension in healthy lifespan and an economic benefit of 7.1 trillion over 50 years.
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• 9/5/24Matt Kaeberlein reflects on "David Sinclair’s Longevity Lie" | 62 - Longevity Reacts #5
In this episode, Matt and Nick react to investigative journalist and author Scott Carney's video describing what he calls "David Sinclair's longevity lie" in the context of David's longevity-focused entrepreneurial ventures. Matt shares his professional history with David, including his early interactions with David in Leonard Guarente's lab at the Massachusetts Institute of Technology (MIT) and scientific differences that emerged after Matt and colleagues were unable to reproduce a key result from David's work pertaining to resveratrol. Their discussion touches on some of David's scientific claims about age reversal, the role of institutions such as Harvard University in regulating scientific integrity, the potential for future interventions in healthspan and longevity, and the importance of separating personal feelings from scientific evaluation.
David, currently a professor in Harvard Medical School's Department of Genetics at the Paul F. Glenn Center for Biology of Aging Research, is a prominent aging researcher whose lab focuses on age-related epigenetic change, cellular reprograming, longevity drug discovery, mitochondrial fitness, reproductive aging, neurodegenerative disease,, and the human secretome. He has received awards including the National Institutes of Health Nathan Shock Award, the Merck Prize, and the Australian Medical Research Medal, and was elected to TIME's 2014 “100 Most Influential People in the World" list. David conducted postdoctoral research at MIT and obtained a PhD in Molecular Genetics at the University of New South Wales.
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!
Matt and colleagues coauthored this paper in 1999 demonstrating that the SIR2 gene regulates yeast lifespan. Upregulating SIR2 extended yeast lifespan by about 30 percent.
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
This paper really kicked off David's sirtuin story. The paper's authors, which included David, developed an assay—a test or an analysis done to figure out the amount or presence of a specific substance or component in a sample—to identify drugs to activate the SIR2 gene and/or sirtuins, a family of proteins that help regulate important processes like metabolism, DNA repair, and stress response in the body. They found that resveratrol and several other compounds activated sirtuins and made yeast live longer.
Substrate-specific Activation of Sirtuins by Resveratrol
Matt and colleagues examined the effects of resveratrol on yeast SIR2 and found that the resveratrol-induced activation of yeast SIR2 was entirely dependent upon the presence of a particular fluorescent group. Without that group, resveratrol no longer had a significant effect on yeast SIR2 activity.
Mechanism of Human SIRT1 Activation by Resveratrol
This paper independently reproduced the findings of Matt and colleagues that resveratrol did not, in fact, affect sirtuin activation. Researchers tested the effects of resveratrol on three enzymes—yeast SIR2, human SIRT1, and human SIRT2—using the same assay that the authors of the original yeast life-extension-by-resveratrol paper developed and presented. They found that resveratrol activated only one of the enzymes, SIRT1. Crucially, it seemed that removing a particular fluorescent group removed the effect of resveratrol on SIRT1, suggesting that the finding was an artifact. The rather mild title of both this paper and Matt's may have contributed to the resveratrol story's persistence in the public consciousness for many years after these findings should have called the molecule's effectiveness as a lifespan extension tool into question.
This study describes the results of a clinical trial that Animal Biosciences, a company that David founded, funded. The clinical trial examined the effects of a therapeutic consisting of an NAD+ precursor and senolytic on dogs with mild to moderate cognitive impairment and reported a significant difference in cognitive impairment as measured by the owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale. In a press release, David made claims about the findings of this study that Matt criticized as dishonest.
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• 8/13/24Scientist Reacts to Greg Doucette's Controversial Take on DEXA Scans | 57 - Longevity Reacts #4
Coach, bodybuilder, and powerlifter Greg Doucette published a video on his Youtube channel discussing what he sees as the shortcomings of DEXA scans and why DEXA scans are not, in fact, the gold standard of body composition measurement. He bases his views on personal experience as well as his interpretation of a 2019 study that examined how closely DEXA and MRI measurements correlate.
In this episode, Matt reacts to Greg's video and presents his own opinion about the validity of DEXA scan measurements. Together with Nick, he discusses what DEXA scans do and don't measure, potential sources of inaccuracy in DEXA scans, honest interpretations of scientific literature, and more.
A DEXA (dual-energy X-ray absorptiometry) scan is an advanced imaging procedure for measuring bone density and composition. DEXA scans utilize two different energy levels of low-dose X-ray beams—one absorbed mostly by soft tissue, and the other absorbed mainly by bone—to differentiate between bone, fat, and lean tissue. In so doing, they provide noninvasive and detailed information about bone health, risk of osteoporosis or fractures, and body composition. While medical practitioners typically perform DEXA scans on the lower spine and hips, they can also perform DEXA scans on the whole body for the purposes of early detection and intervention.
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!
This is the paper upon which Greg bases his argument that DEXA scans are not necessarily useful tools for body composition measurement (though he does also state his opinion that studies are wrong half the time). This study examines the correlation between magnetic resonance imaging (MRI) and DEXA scans measurements of lean mass, and argues that while the cross-sectional correlation between the measurements is strong, the correlation of percent change over time is modest and thus DEXA scans may not be able to detect lean mass changes over time to a degree of accuracy necessary for use in clinical trials.
What Is a DEXA Scan and How Can It Help You?
This is an introduction to DEXA scans that covers the history of DEXA scans, how DEXA scans work, what happens during a DEXA scan, and how DEXA scans compare to imaging techniques such as CT scans, magnetic resonance imaging (MRI) scans, and x-rays.
Unexpected DEXA Scan Results? Here are Some Potential Causes:
You may have gotten your DEXA scan results back and balked at what you saw. This list addresses some possible reasons for DEXA scan surprises.
This study found a high correlation between visceral fat content measured by DEXA scans and the actual excised visceral fat content of mice, suggesting that DEXA scans are accurate tools for noninvasive fat distribution measurement.
This list of FAQs covers many questions people have about DEXA scans, including how much radiation exposure we receive from DEXA scans, height and weight limits, the safety of DEXA scans for pregnant wome, and more.
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• 7/31/24A Longevity Breakthrough w/ Yamanaka Factor "Rejuvenation Cocktail?" | 53 - Longevity Reacts #3
In June 2024, the Aspen Ideas Festival held a three-day health-focused event in which speakers discussed new breakthroughs, policy developments, and possible futures in healthcare. "You Can Live Longer!" was a panel discussion during the festival that consisted of Altos Labs founder and chief scientist Rick Klausner, Cradle CEO and cofounder and venture capitalist Laura Deming, BioAge Labs CEO and cofounder Kristen Fortney, and NPR News Food and Health Correspondent Allison Aubrey discussing developments in the longevity field.
In this episode, Matt and Nick react to the panel discussion and discuss the potential of epigenetic reprogramming for improving organ transplants and reversing organ aging, the limitations of current techniques, the relevance of aging models in disease research, and more.
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!
The panel discussion that Matt and Nick discuss in this episode took place at the 2024 Aspen Ideas Festival, a gathering of thinkers from different fields in an immersive event exploring new ideas and innovations. The three speakers, each of them leaders in different niches of the longevity space, discuss a wide range of topics, including new drugs in the pipeline that target healthy aging, the manipulability of the cellular aging process, and the functional significance of biological age clocks. They also discuss talent entering the longevity field and difficulties convincing investors to pay attention to aging in years past.
In 2006, Kazutoshi Takahashi and Shinya Yamanaka published this paper reporting four key transcription factors—Oct3/4, Sox2, c-Myc, and Klf4—whose overexpression induced mouse fibroblasts to return to their pluripotent, or immature, state. We now refer to these four factors as "Yamanaka factors". Transplanting the pluripotent cells that arose from Yamanaka factor introduction gave rise to certain adverse effects such as tumors.
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
This paper, which Takahashi and Yamanaka coauthored along with several collaborators, demonstrated that the four Yamanaka factors described in the previous paper also worked to induce a pluripotent cell state in adult human dermal fibroblasts. The Yamanaka-factor-induced pluripotent cells shared many features with human embryonic stem cells. The authors acknowledged the increased risk of tumor formation as a result of Yamanaka factor reprogramming.
This article covering the Aspen Ideas Festival panel speculates that Altos Labs, a Jeff Bezos-backed company whose founder and chief scientist is panelist Rick Klausner, has achieved positive results with a "reprogramming cocktail" based on the Yamanaka factors.
Mice are some of the most common animal models researchers use for studying human aging. This short article provides a helpful comparison of mouse and human life phases and aging, and shows that the correlation between mouse and human aging is not linear. It proposes an age at which "old mice" best correlate with "old humans", an important metric to consider in studies of mouse aging aimed at eventual translation to human aging.
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• 7/23/24Longevity Scientist Critiques Mike Israetel's "Exercise Scientist Critiques" | 51 - Longevity Reacts
Entrepreneur and competitive bodybuilder Mike Israetel recently released a video discussing Bryan Johnson's anti-aging protocol. Towards the end of the video, he gives us his take on the "big rocks" that account for the bulk of our longevity.
In this episode, Matt reacts in real time to his first watch of this end portion of Mike's video. Together with Nick, he goes over Mike's suggestions about diet, drugs, body composition, and supplements and provides some additional context and nuance to each recommendation where he sees fit.
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!
Renaissance Periodization
Mike Israetel's company, Renaissance Periodization, offers diet and exercise consultations and coaching as well as a hypertrophy app aimed at helping people get bigger muscles. This is the company's Youtube channel. The channel publishes videos featuring diet, exercise, and mindset tips, critiques of workout programs, and more.Big mice die young: early life body weight predicts longevity in genetically heterogeneous mice
This study found that mice with a smaller body size outlived those with a larger body size. This association was present in both male and female mice and was stronger for weights taken earlier rather than later in life, suggesting that low body weight at earlier ages is particularly advantageous for mouse longevity. The authors hypothesize that body weight is likely a surrogate measure of biological changes that influence weight as well as later life outcomes.Is height related to longevity?
Good news for short people: according to this study, rates of diet-related chronic disease are lower in people of shorter height, especially after middle age. Shorter people also tend to live longer. Data from centenarians—people who reach 100 years of age—bear this finding out: the study reported that Japanese centenarians were around 10 centimeters shorter than 75 year-olds, and that Hungarian centenarians had an average height of 154cm (about five feet one inch).Metabolite accumulation from oral NMN supplementation drives aging-specific kidney inflammation
Matt and George Sutphin discussed this preprint in a recent episode. The preprint authors found that, contrary to their expectations that NAD+ boosters would help ameliorate kidney aging in mice, an NAD+ booster actually led to increased levels of potential kidney damage markers. These results do not conclusively demonstrate a negative effect of NAD+ boosters on kidney health, but there's smoke there, as Matt says, and the finding is worth further investigation.Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
How might NAD+ precursors such as NMN affect people? This study reported that overweight or obese prediabetic women who had undergone menopause showed improved muscle insulin sensitivity and insulin signaling with NMN supplementation. They also experienced higher levels of downstream muscle NMN metabolites, or nicotinamide byproducts. -
• 7/18/24Longevity Scientist Reacts to Bryan Johnson's "I Edited My DNA To Live Forever" |50-Longevity Reacts
Last month, entrepreneur and venture capitalist Bryan Johnson released a Youtube video detailing his trip to Prospera, Honduras to receive follistatin gene therapy from the Minicircle Gene Therapy clinic. Bryan describes Minicircle's gene therapy as "a pioneering technology with the potential to improve muscle and strength, slow the speed of aging, and many more benefits".
In this episode, Matt reacts in real time to his first watch of Bryan's video and responds to Nick's questions about various topics that come up along the way. He provides a primer on gene therapy and its potential as a longevity intervention, discusses the clinical evidence for follistatin's effects on humans and model organisms, and goes through several things one might want to consider when deciding whether to partake in a new therapy. He also gives his honest take on "offshore medicine"—medicine performed in countries that lack the regulatory oversight of the United States Food and Drug Administration—and discusses potential mechanisms for safely offering experimental therapies in the United States.
Follistatin is a glycoprotein that functions as a potent inhibitor of several members of the TGF-beta superfamily, particularly activin and myostatin. It is involved in various physiological processes, including muscle growth and development, reproduction, and inflammation. By binding to these proteins, follistatin prevents them from interacting with their receptors, thereby regulating their activity.
Minicircle Gene Therapy https://minicircle.ioCheck 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!
Here's Minicircle's website if you'd like to check out the company's claims, follistatin primer, and more for yourself. The website includes the company's answer to "will this turn me into a superhuman?".
What is Gene Therapy?
This is a quick primer on gene therapy that the United States Food & Drug Administration has released. It covers potential mechanisms for manipulating gene expression in humans as well as some of the products currently available to do so.Plasmid delivery of follistatin gene therapy safely improves body composition and lowers extrinsic epigenetic age in sex- and age-diverse adult human subjects
This paper, sponsored by Minicircle Gene Therapy, presents the results of a clinical trial demonstrating the efficacy of follistatin gene therapy on body composition and extrinsic epigenetic age in humans. Mean lean mass increased by 1.96 lbs, with a maximum increase of 12.15 lbs, and mean body fat reduction was 0.87 percent. The study reported mild trends in inflammatory markers, glucose metabolism, and cholesterol, none of which were significant. Participants did not experience severe adverse effects related to the therapy.New intranasal and injectable gene therapy for healthy life extension
Matt mentions this paper in the podcast as a piece of research that has received some criticism for several reasons, among them a small sample size of mice in each treatment group. This study tested the efficacy and safety of a viral vector for delivering telomerase reverse transcriptase and follistatin gene therapy, and found lifespan extension effects for both therapies of 41.4 percent and 32.5 percent respectively. The paper also describes other observed effects of one or both gene therapies, including telomere length increases in some tissues, improvements in hair loss and texture, weight loss prevention, improved motor coordination, and preserved mitochondrial integrity.Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice
A senolytic is an agent that selectively clears senescent cells. This paper describes vaccination as a potential delivery agent for a senolytic, enabling delivery to specific sites and the avoidance of off-target effects. The researchers suggest that a vaccination targeted at glycoprotein nonmetastatic melanoma protein B (GPNMB), a protein that is enriched in senescent cells, increases mouse lifespan and improves various aging-associated phenotypes such as atherogenesis.