Key Moments
171- Longevity science: caloric restriction studies, aging biomarkers & possible longevity molecules
Key Moments
Longevity science explored: caloric restriction, biomarkers, animal models, and human studies.
Key Insights
Steve Austad's unconventional journey shaped his unique perspective on aging research.
Laboratory animals, particularly mice, differ significantly from their wild counterparts, impacting research validity.
Caloric restriction (CR) shows longevity benefits in animals, but human studies reveal challenges with adherence and potential downsides.
Dietary composition, especially sugar intake, may be as crucial as calorie reduction.
Sex differences in longevity are significant and likely rooted in complex biological factors beyond behavior.
Developing reliable biomarkers of aging is critical for advancing human longevity research.
A SCIENTIST'S UNCONVENTIONAL PATH
Steve Austad's early life was marked by a nomadic upbringing due to his father's union traveling card, exposing him to diverse educational experiences. Initially drawn to mathematics and literature, he eventually found his calling in biology, influenced by early encounters with nature and a series of unexpected life experiences. These included driving a taxi in 1970s New York, a stint as a lion tamer, and a near-fatal lion attack, all contributing to a unique, interdisciplinary approach to scientific inquiry.
THE LABORATORY ANIMAL DILEMMA
A significant focus of the discussion is the divergence between laboratory animals and their wild counterparts. Austad highlights how extensive inbreeding and selection over generations have created 'genetically identical' mouse strains that are dramatically different from wild mice in size, reproduction, and susceptibility to disease. This genetic uniformity, while useful for controlled genetic studies, raises concerns about the translational relevance of findings to human and wild animal biology, which is far more genetically diverse.
CALORIC RESTRICTION: PROMISE AND PITFALLS
The conversation delves into caloric restriction (CR) as a key area of longevity research. While studies in rodents and even primates (like the Wisconsin National Primate Research Center study) show significant lifespan and healthspan benefits, human trials present challenges. Achieving substantial calorie reduction is difficult for humans, and while some improvements in cardiovascular markers are observed, potential downsides like reduced bone mineral density and muscle mass loss emerge, particularly in extreme CR practitioners.
THE ROLE OF DIET QUALITY
The nuanced findings from the rhesus macaque studies underscore the importance of diet quality beyond mere calorie reduction. The contrast between the Wisconsin study (using purified, high-sucrose diets) and the NIA study (using natural ingredients with low sucrose) suggests that the detrimental effects of a poor diet, particularly high sugar intake, may significantly influence CR outcomes. The Bethesda group's controls, eating a healthier diet, lived longer and healthier lives than the restricted group in Wisconsin, highlighting the impact of diet composition.
SEX DIFFERENCES AND LONGEVITY
A striking observation is the consistent survival advantage of women across all age groups. While behavioral factors, such as men's propensity for risk-taking, contribute, biological factors are likely more significant. Hypotheses explored include the protective effect of a second X chromosome in women and potential incompatibilities between male nuclear and mitochondrial genomes. The discussion emphasizes that these sex differences are profound and may necessitate sex-specific approaches to longevity interventions.
THE QUEST FOR BIOMARKERS AND FUTURE INTERVENTIONS
The conversation concludes by addressing the critical need for reliable biomarkers of aging. While epigenetic clocks show promise and rapid changes, their short-term volatility and susceptibility to manipulation raise questions about long-term clinical utility. The focus shifts to the proteome and metabolome as more stable indicators. The discussion also touches upon potential longevity molecules like Rapamycin and Metformin, the challenges in translating animal findings to humans, and the significant public health focus on obesity, which can overshadow longevity research.
Mentioned in This Episode
●Supplements
●Organizations
●Studies Cited
●Concepts
●People Referenced
Common Questions
Steve started in math, then switched to English, aiming to be a novelist. After working as a taxi driver and even a lion trainer, a significant injury from a lion led him to graduate school. While studying social birds, he noticed opossums aged incredibly quickly, sparking his lifelong interest in the biology of aging.
Topics
Mentioned in this video
A researcher involved in both the NIA and University of Wisconsin primate caloric restriction studies.
A researcher who demonstrated that fasting for a few days significantly improved recovery from lethal injuries in mice.
An immunologist who extensively studied caloric restriction in mice and was a participant in the Biosphere 2 experiment.
A famous American novelist, mentioned by Steve as his literary aspiration during his college years.
Conducted an analysis that equated the diet of the Wisconsin monkeys to human fast food consumption.
Another researcher who followed up on caloric restriction in rats, interested in understanding the mechanisms of aging.
Host of The Drive podcast and interviewee's friend, who introduces the guest and guides the discussion on longevity science.
An actress whom Steve had a crush on as a child; he ended up living in her house while working as a lion trainer.
A nutritionist at Cornell who conducted pioneering dietary restriction experiments in the 1930s, discovering that feeding animals less made them live longer.
A researcher known for his strong advocacy of Metformin's benefits, even for healthy individuals, which differs from Steve's more skeptical view.
A genetic condition in men with XXY chromosomes, mentioned in the context of X-chromosome redundancy and its potential impact on longevity.
A neurodegenerative disease, noted as the only major cause of death where women do not die at a lower rate than men, leading to a hypothesis about an autoimmune component.
A genetic condition in women with only one X chromosome (XO), noted for definitively shorter lifespans, supporting the idea of X-chromosome benefits.
A gene that when suppressed can have multiple health benefits, which can also be achieved through fasting periods.
The U.S. regulatory body that makes it challenging to conduct trials with longevity drugs in healthy people due to safety concerns for long-term use.
Proposed funding for a clinical trial to look at Rapamycin as a preventative for kidney cancer recurrence, but the funding was unsuccessful.
A long-running research project in East Africa that had just ended when Steve went to graduate school, hoping to study lions there.
One of the three institutions involved in the CALERIE studies, which published results in the later phase.
One of the three institutions involved in the CALERIE studies.
The institution where Clive McCay conducted his early, landmark caloric restriction experiments.
One of two groups that conducted the largest and most expensive longevity experiments on rhesus macaques, focusing on caloric restriction.
One of the three institutions involved in the CALERIE studies.
A group of individuals who practice extreme caloric restriction inspired by rodent studies, often called 'cronies'.
The university where Steve did his undergraduate studies and played soccer.
One of two groups that conducted the largest and most expensive longevity experiments on rhesus macaques, focusing on caloric restriction.
Two human studies on caloric restriction, one short-term (6 months) and one longer-term (2 years), that showed people struggled to achieve high levels of restriction consistently.
Steve's first faculty position after his postdoc, where he began his aging research career.
An FDA-approved drug identified as having the most potential for geroprotection based on mouse data, especially in sex-specific and dose-dependent ways.
An SGLT2 inhibitor tested in the ITP, suggesting its benefits on longevity might be related to glucose kinetics rather than caloric intake.
A molecule that has shown unbelievable success in male mice in the ITP, but is not FDA approved for longevity.
An FDA-approved drug identified as having the most potential for geroprotection based on human data, despite weak mouse data.
A Rapamycin analog that has been tested in humans for enhancing vaccine response to influenza, showing promise at lower doses with fewer side effects.
A class of drugs showing remarkable human data on kidney failure, all-cause mortality, and heart failure, with potential benefits in longevity that may not be solely due to caloric reduction.
The city Steve moved to after college to gain life experiences for novel writing, working as a taxi driver in the mid-1970s.
Location of a compound north of Los Angeles where Steve was injured by a lion, prompting him to reassess his career.
The place where Steve got a job as a lion trainer for a movie crew, which he found less interesting than the animals themselves.
An island off the coast of Georgia where Steve studied opossums in a low-predator environment.
Mentioned as an example of how dangerous New York City was in the 1970s, where one could get robbed in daylight.
Described as a dangerous area in New York City in the 1970s where many cab drivers refused fares.
The city Steve moved back to after his taxi driving years and before his Hollywood animal training career.
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