In this Part 1 episode, Matt and Brian Kennedy cover various aspects of aging research, including the connection between the immune system and aging, the role of inflammation, the potential of supplements and wearables in healthspan, and insights on longevity interventions. They also discuss the challenges in the field regarding clinical practices, the influence of AI on aging research, and personal experiences with health optimization.

This is Part 1 of a two-part series—stay tuned for even more in the next episode.

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://pubmed.ncbi.nlm.nih.gov/38151871/

Matt and Brian talk about supplementing vitamin D as a healthy aging intervention, specifically when supplementing deficiencies. The RESORT study was a prospective, observational, and longitudinal analysis of 1,328 geriatric rehabilitation inpatients highlighting the importance of supplementing vitamin D in individuals that are deficient and associations with improved age-related outcomes. Researchers measured vitamin D levels near the time of rehabilitation admission, categorizing them as sufficient, insufficient, and deficient. The study examined associations between vitamin D levels and adverse health outcomes, including institutionalization at three months post-discharge, in-hospital mortality, and post-discharge mortality. Patients not using vitamin D supplements and having insufficient or deficient 25(OH)D levels exhibited significantly higher in-hospital mortality compared to those on supplementation. This study highlights the importance of vitamin D in physiological resilience and suggests that monitoring and addressing vitamin D status is crucial to potentially mitigate adverse health outcomes 

Age Reversal & Thymus Rejuvenation TRIIM-X 2024 Update | Dr Greg Fahy Full Interview

Matt discusses his thoughts on the promise and relative safety of the putative gerotherapeutic cocktail including growth hormone, metformin and DHEA, especially considering the preliminary results from the Thymus Regeneration, Immunorestoration, and Insulin Mitigation (TRIIM) trial demonstrating partial thymus regeneration, improvements in immune markers, glucoregulatory improvements, and reversal of epigenetic biological age clock score. This Modern Healthspan podcast is an interview with Dr Greg Fahy, principal investigator of the TRIIM-X trial (12 month follow up to TRIIM), going through the latest updates from the study which assesses the effects of personalized doses of the above interventions on biomarkers for epigenetic aging and immunosenescence, as well as clinical measures and risk factors for conditions such as physical frailty, cancer, cardiovascular disease, diabetes, dementia, and infectious diseases, including flu and COVID-19. 

https://pmc.ncbi.nlm.nih.gov/articles/PMC9810745/

Matt and Brian discuss the significant role of post-menopause on accelerating the biological aging process and contributing to age-related diseases. This review coauthored by Brian highlights progress in understanding the biology of ovarian aging and the potential of manipulating aging-related pathways in animal models for prolonging female reproductive lifespan and healthspan. Further, slow aging of the reproductive system could delay menopause, thereby reducing the incidence of age-related diseases like osteoporosis, cardiovascular disease, and Alzheimer’s while improving overall health in aging women. The review also highlights the personal and social impacts of addressing reproductive decline as it influences women's life choices, often forcing a balance between career aspirations and family planning. Advancements in reproductive longevity research could provide women with greater autonomy over their reproductive health, aligning biological and health outcomes with personal and professional goals. 

https://www.biorxiv.org/content/10.1101/2022.02.06.479300v1

Brian discusses Peter Fedichev’s theory of aging when explaining his perspective on why addressing each hallmark of aging is an insufficient strategy for significantly improving healthy longevity due to the substantial number of permutations and random nature of age-related damage accumulation. This paper highlights Peters’ theory of aging and introduces the novel concept of "thermodynamic biological aging" (tBA), which quantifies the accumulation of random variations in physiological state variables over time. Specifically, this model measures changes in entropy through tracking changes in various biological processes associated with energy usage and heat production (a function of increasing entropy). The study found that tBA increases with chronological age and leads to a linear and irreversible drift in variables associated with physiological health, contributing to the gradual decline in bodily functions associated with aging. The researchers also found that the accumulation of tBA correlates with an exponential rise in the risk of chronic diseases and mortality, aligning with observed patterns in aging populations. The study suggests that the entropic nature of aging imposes fundamental constraints on the potential for age reversal. Despite limitations in reversing aging, the research highlights universal features in the transition between different physiological health states that could be targeted to modulate the rate of aging. This suggests that interventions may be developed to slow down aging processes, thereby extending healthspan and lifespan.

Epigenetic age oscillates during the day - Koncevičius - 2024 - Aging Cell - Wiley Online Library

Matt and Brian discuss the complexities of interpreting epigenetic aging clock results given research suggesting epigenetic readouts fluctuate within a 24 hour cycle. This study highlights how epigenetic age fluctuates throughout the day, suggesting a circadian rhythm influence on biological aging. Using DNA methylation data, the study tracks epigenetic age variations across different times. The findings indicate a rhythmic pattern, with epigenetic age fluctuating by several years over a 24-hour cycle. This highlights the potential importance of daily biological rhythms in understanding the epigenetic aging processes and the impact of time-of-day on the collection, interpretation, and standardization of biological age clocks within both research and the commercial space. Brian highlights an interesting concept that the fluctuating nature of epigenetic biological age natures may even reflect the underlying, malleable nature of the biological aging process.