An Interview with Matthew O'Connor, as Underdog Pharmaceuticals Secures Seed Funding

Matthew O'Conner presented at Undoing Aging earlier this year on the startup biotech company Underdog Pharmaceuticals. The company is spinning out of the SENS Research Foundation (SRF), based on research conducted by the scientific team there in recent years. The company is focused on a class of molecule known cyclodextrins, and have candidates capable of efficiently binding and sequestering 7-ketocholesterol. This form of oxidized cholesterol is of great importance to the progression of atherosclerosis, and possibly other age-related conditions as well. In the case of atherosclerosis, the presence of oxidized cholesterols, and particularly 7-ketocholesterol, causes the macrophage cells, which are responsible for clearing out cholesterol from blood vessel walls, to become dysfunctional and inflammatory. Remove the 7-ketocholestrol, and the problem should largely go away. I'm pleased to note that Underdog Pharmaceuticals has secured nearly $4 million in seed funding, and is thus well set to move ahead with the clinical development of this approach over the next few years. I would hope that this will be one of numerous biotech companies focused on rejuvenation research to emerge directly from the SENS Research Foundation in-house programs, joining the many others that have emerged within the broader network of researchers and entrepreneurs interested in tackling causes of aging. To mark the occasion, I recently had the chance to chat with Matthew O'Conner about Underdog ...
Source: Fight Aging! - Category: Research Authors: Tags: Healthy Life Extension Community Source Type: blogs

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, the enhanced mice live somewhat longer than their unmodified peers, though not as much longer as is the case for the application of telomerase gene therapy. The mice do also exhibit reduced cancer risk, however. The scientists here class telomere shortening as a cause of aging, which is not a point universally agreed upon. Reductions in average telomere length in tissues looks much more like a downstream consequence of reduced stem cell activity than an independent mechanism. Researchers obtain the first mice born with hyper-long telomeres and show that it is possible to extend life without any geneti...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Discussion of Developmental Effects on Aging Microtubule Function and Longevity in Nematodes Quantifying the Correlation Between Poverty and Faster Pace of Aging Matthew O'Connor Presenting on Underdog Pharmaceuticals at Undoing Aging 2019 https://www.fightaging.org/archives/2019/09/matthew-oconnor-presenting-on-underdog-pharmaceuticals-at-undoing-aging-2019/ Here Matthew O'Connor of the SENS Research Foundation talks about the research that led to founding of Underdog Pharmaceuticals, a biotech startup incubated by the foundation to commercialize a means of targeting 7-ketocholesterol in atheroscleros...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, researchers studied 438,952 participants in the UK Biobank, who had a total of 24,980 major coronary events - defined as the first occurrence of non-fatal heart attack, ischaemic stroke, or death due to coronary heart disease. They used an approach called Mendelian randomisation, which uses naturally occurring genetic differences to randomly divide the participants into groups, mimicking the effects of running a clinical trial. People with genes associated with lower blood pressure, lower LDL cholesterol, and a combination of both were put into different groups, and compared against those without thes...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We examined human lung tissue from COPD patients and normal control subjects, and found a substantial increase in p16-expressing alveolar cells in COPD patients. Using a transgenic mouse deficient for p16, we demonstrated that lungs of mice lacking p16 were structurally and functionally resistant to CS-induced emphysema due to activation of IGF1/Akt regenerative and protective signaling. Fat Tissue Surrounds Skeletal Muscle to Accelerate Atrophy in Aging and Obesity https://www.fightaging.org/archives/2019/09/fat-tissue-surrounds-skeletal-muscle-to-accelerate-atrophy-in-aging-and-obesity/ Researchers her...
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In conclusion, in the absence of obesity, visceral adipose tissue possesses a pronounced anti-inflammatory phenotype during aging which is further enhanced by exercise. Methods of Inducing Cellular Damage are Rarely Relevant to Aging, and the Details Matter https://www.fightaging.org/archives/2019/08/methods-of-inducing-cellular-damage-are-rarely-relevant-to-aging-and-the-details-matter/ One of the major challenges in aging research is determining whether or not models of cellular or organismal damage and its consequences are in any way relevant to the natural processes of aging. One can hit a brick with...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We examined 9293 individuals from the Copenhagen General Population Study using nuclear magnetic resonance spectroscopy measurements of total cholesterol, free- and esterified cholesterol, triglycerides, phospholipids, and particle concentration. Fourteen subclasses of decreasing size and their lipid constituents were analysed: six subclasses were very low-density lipoprotein (VLDL), one intermediate-density lipoprotein (IDL), three low-density lipoprotein (LDL), and four subclasses were high-density lipoprotein (HDL). Remnant lipoproteins were VLDL and IDL combined. Mean nonfasting cholesterol concentration was 72...
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In this study we show, for the first time, significant alterations in cholesterol efflux capacity in adolescents throughout the range of BMI, a relationship between six circulating adipocyte-derived EVs microRNAs targeting ABCA1 and cholesterol efflux capacity, and in vitro alterations of cholesterol efflux in macrophages exposed to visceral adipose tissue adipocyte-derived EVs acquired from human subjects. These results suggest that adipocyte-derived EVs, and their microRNA content, may play a critical role in the early pathological development of ASCVD. Commentary on the Developing UK Government Position on Hea...
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This study elucidates the potential to use mitochondria from different donors (PAMM) to treat UVR stress and possibly other types of damage or metabolic malfunctions in cells, resulting in not only in-vitro but also ex-vivo applications. Gene Therapy in Mice Alters the Balance of Macrophage Phenotypes to Slow Atherosclerosis Progression https://www.fightaging.org/archives/2019/07/gene-therapy-in-mice-alters-the-balance-of-macrophage-phenotypes-to-slow-atherosclerosis-progression/ Atherosclerosis causes a sizable fraction of all deaths in our species. It is the generation of fatty deposits in blood vessel...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study sought to investigate what could be learned from how these men have fared. The men were born in 1925-1928 and similar health-related data from questionnaires, physical examination, and blood samples are available for all surveys. Survival curves over various variable strata were applied to evaluate the impact of individual risk factors and combinations of risk factors on all-cause deaths. At the end of 2018, 118 (16.0%) of the men had reached 90 years of age. Smoking in 1974 was the strongest single risk factor associated with survival, with observed percentages of men reaching 90 years being 26.3, 25.7, ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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