12/10/24

Longevity 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.

#4810 DIAGNOSTIC AND THERAPEUTIC IMPACTS OF AIM ON END-STAGE KIDNEY DISEASE | Nephrology Dialysis Transplantation | Oxford Academic

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%.

Substantial Health and Economic Returns From Delayed Aging May Warrant a New Focus for Medical Research - PMC

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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