Summary
In this podcast episode, the host interviews a guest who shares their unique background and journey to where they are today. The guest initially went to college as a math major but switched to English and aspired to become a novelist. They moved to New York to accumulate experiences for their writing and ended up driving a taxi at night to have unique experiences. The guest shares some interesting and sometimes dangerous experiences they had as a taxi driver in New York in the mid-1970s. Later, they got involved in training animals after helping transport a lion to Hollywood. They were offered a job as a lion trainer and ended up living with actress Tippy Hedren while taking care of the lions. However, they were eventually injured by a lion and had to spend time in the hospital, which led them to go back to graduate school.
The conversation then turns to the history of dietary restriction research in animals and its potential application to human aging. The speaker discusses the work of researchers such as Roy Walford and Ed Masro, who studied the effects of dietary restriction on mice and rats. The speaker also mentions the Biosphere 2 experiment, which inadvertently tested the effects of dietary restriction on humans. The conversation then turns to the differences between rats and mice in terms of genetic diversity and their potential use in aging research. The speaker also discusses the Wisconsin NIA experiment, which aimed to replicate the effects of dietary restriction on primates. The experiment had mixed results, with different conclusions drawn by the two research groups involved.
The context discusses the impact of calorie restriction on the lifespan of animals and humans. The speaker explains that calorie restriction has been studied in mice and humans, with mixed results. While it has been shown to improve cardiovascular risk factors and lower glucose and insulin levels, it can also lead to negative effects such as lower bone mineral density and muscle mass. The speaker mentions a group called the "cronies" who practice extreme calorie restriction and have good cardiovascular risk factors but suffer from low bone mineral density and negligible sex hormones. The impact of calorie restriction on cognitive function and immune function is not clear.
The discussion revolves around the differences in lifespan between men and women, and the potential reasons for these differences. One theory is that women have a redundant set of genes on their second X chromosome, which can compensate for any defective genes on the other X chromosome. However, men with Klinefelter's syndrome (XXY) also have this redundancy, but do not live as long as women. Another theory is that there may be an issue of compatibility between the mitochondrial genome and the nuclear genome, as mitochondrial genomes are only passed down through females. The discussion also touches on the differences in biomarkers of aging between men and women, as well as the limitations of using mice as a model for studying these differences. Finally, there is some debate over the usefulness of epigenetic data as a biomarker for aging, with one participant expressing skepticism about its practical value.
The speaker discusses the potential of using proteome and metabolome to find markers for longevity. However, the computational complexity and lack of commercial interest make it difficult to invest in this area. The speaker also talks about a bet made 20 years ago about the first 150-year-old human, and how the key to longevity may lie in developing molecules that fundamentally change the rate of aging. The speaker suggests that a combination of existing molecules such as rapamycin and metformin may be the most helpful for gero protection. However, clinical trials on completely healthy people are difficult to conduct, and dosing rapamycin in a longevity trial is a challenge.
