Longevity Scientists Answer 30 MORE of Your Health & Longevity Questions | PART 2
In this Q&A, Matt and Brian Kennedy cover a range of topics on caloric restriction, lifespan studies, interventions like rapamycin, and the importance of control groups in research. They critique the validity of certain longevity claims, discuss the complexities of aging mechanisms, and question the effectiveness of supplements. The conversation also touches on dietary impacts, the role of exercise, and the significance of personalized medicine in aging research, emphasizing the need for careful interpretation of scientific data.
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 Brian talk about being cautious about interpreting the results from mouse lifespan studies when evaluating the potential effectiveness of a putative longevity intervention. This research study performed a comprehensive reanalysis of mouse lifespan studies to assess how the lifespan of control groups influences the perceived efficacy of longevity interventions. The analysis revealed that interventions appeared more effective in studies where control groups had shorter lifespans. This suggests that the relative efficacy of longevity treatments may be overstated when control animals are inherently short-lived. The researchers (including Matt and Brian) propose that individuals apply the “900 day rule” as one important criteria to safeguard against over-interpreting the results of lifespan studies, as this is the average lifespan of control mice.
Matt and Brian discuss the data suggesting chronic alcohol consumption is detrimental to longevity but also the body of preclinical literature demonstrating low dose alcohol consumption improves lifespan in multiple preclinical studies across different model organisms. This perspective piece coauthored by Brian explores how low-dose alcohol consumption may confer health benefits through epigenetic mechanisms, particularly histone acetylation. The authors discuss how alcohol is metabolized into acetate, which is then converted to acetyl-CoA, a key substrate in the histone acetylation process which can lead to changes in gene expression that may have health-promoting effects. They suggest that this mechanism could underlie some of the observed benefits associated with low to moderate alcohol consumption, such as improved cardiovascular health. This perspective highlights the complex role of alcohol in health and disease, emphasizing the importance of dosage and likely also physiological context.
This systematic review evaluated 52 studies involving glycine administered over periods ranging from up to 14 days in healthy individuals to up to 4 months in diseased populations to elucidate effects on various physiological systems and healthspan metrics. Glycine's effects on cognitive health were most robust, with marked improvements in emotional health and sleep in normative aging individuals.The authors highlight that dietary glycine has been associated with increased healthy lifespan in model organisms and may decrease inflammation in humans, suggesting its potential as a geroprotective agent. The authors highlight the necessity for larger, long-term studies with robust designs in healthy populations to examine glycine's effects on preventing, delaying, or reversing aspects of the aging process.
https://link.springer.com/article/10.1007/s11357-023-01011-0
Brian discusses his enthusiasm for the compound astaxanthin as a putative geroprotective intervention, in large part based on positive feedback he’s received from several different clinicians on its positive effects on the health of their patients. While Matt is encouraged by the preclinical data and clinical anecdotes, he emphasizes caution as astaxanthin is still relatively understudied. This research paper from the Intervention Testing Program highlights the differential effectiveness of several different gerotherapeutic candidates for extending lifespan, the popular senolytic fisetin had no effect on lifespan while the anti-nausea medication meclizine extended median lifespan by 8% and astaxanthin extended median lifespan by 12%, both in male mice. This highlights the modest gains in lifespan and sex-specificity observed in preclinical studies.
Matt discusses how the pro-longevity benefits of reduced IGF-1 signaling seen in small dogs may not be entirely due to effects on body size and energetic efficiency. This research study authored by Derek Huffman demonstrates that mice genetically modified for reduced IGF-1 signaling slightly extends lifespan, regardless of body size. Further, age-specific mortality rates were reduced in IGF-1-deficient mice, particularly in late life, indicating an improvement in the typical exponential increase in mortality observed in aging populations.
