Glow & Thrive Longevity Mocktail
Enjoy this month’s research and news roundup! Here the summary from key papers I’ve been interested in lately, more detail below:
Yes, yes, yes: intensive lifestyle interventions (4 papers); omega-3 fatty acids and exercise all WORK on preventing and/or reversing cognitive impairment, including in those with genetic risk (including APOE4). Do adipocytes house epigenetic memory leading to the inevitable weight regaining phenomenon we have long seen? The longevity potential of phytonutrients (you know I am bullish here!). And what about that wildly popular Nature Aging paper on aging happening in two bursts—am I hanging up the towel when I hit 60? (Short answer: no.)
After a whopping 246,507,456,400 data points collected over a median of 1.7 years, can we say that accelerated aging happens in 2 bursts (age 44 and 60)?
At a glance, two hundred forty-six billion, five hundred seven million, four hundred fifty-six thousand, four hundred could strike one as a data-heavy analysis (and upon closer inspection, it still does). Proteomics, lipidomics, metabolomics, transcriptomics, cytokines, standard labs, plus skin, stool, and nasal microbiome specimens were taken from only 108 people. Phew. The first take-home finding? Researchers discovered that aging isn’t a linear event; there appear to be two bursts (crests) happening in middle age. The first burst, occurring around 44, is associated with metabolic slowdowns, connective tissue changes, and fatty tissue shifts that contribute to weight gain and rising cholesterol, while around 60, immune system decline, kidney function reduction, and hormonal shifts accelerate aging markers like decreased vitality and skin quality.
Despite intriguing insights, the study’s small sample size, nonhomogeneous population, and limited data collection period underscore the need for further research, which they acknowledge. This kind of data collection might allow them to build an aging clock that will rival the JILA—or at least may penetrate the aging phenomenon in a way no other clock has done to date. In the end, we have good tools (with more on the way) in functional medicine, epigenetics, and longevity to maintain healthy resilience around the predictable changes they identify. And so, while this study may help unpack our understanding of the aging phenomenon, it also validates what we already know.
The Longevity Potential of Natural Phytochemicals
Anyone familiar with our work knows we are strong advocates for all things phytochemical, particularly polyphenols. These wunderkinds are epinutrient superstars. As I believe the evidence supports, sweet-talking gene expression through a focus on epinutrient and “epilifestyle” habits is one of our strongest tools in the quest for healthy longevity. A recent review in the Journal of Agricultural and Food Chemistry reinforces this thinking (if slightly indirectly). The review analyzed 210 anti-aging phytochemicals, including polyphenols, flavonoids, alkaloids, and terpenoids, highlighting their ability to favorably influence the hallmarks of aging pathways, including autophagy, nutrient sensing, gut microbiota, genomic instability, ROS, and mitochondrial function, among others. The authors suggest that in some cases, polyphenols within the food matrix may be better absorbed and utilized, with at least some demonstrating benefits akin to caloric restriction. And again, might we discover that phytochemicals work their magic, as described in this review, most powerfully by acting directly on the epigenome?
Do Your Fat Cells Have Epigenetic Memory?
We know our cellular memory can house trauma (generationally, even!) or a bias towards proinflammation (or anti-inflammation); and resilience is also likely housed in the epigenome. So, it didn’t come as a wild surprise to me that adipocytes could retain epigenetic memory around obesity, biasing the body toward returning to a previous, higher weight. Even after weight loss, the body may hold onto its previous state, which can contribute to rebound weight gain.
Preliminary research supports this idea, with studies in mice showing that epigenetic changes persist in fat cells post-weight loss, priming them for rapid weight regain when re-exposed to a high-fat diet. Similarly, limited human data hints at comparable patterns, though further research is needed. This aligns with broader concepts of epigenetic memory seen in generational PTSD and ACE (Adverse Childhood Experiences). Understanding these mechanisms may pave the way for targeted therapies to erase or modify this epigenetic memory, potentially improving long-term weight management outcomes. While promising, the findings remain preliminary and underscore the need for more robust research.
Link to paper: HERE.
Overwhelming Evidence: Diet & Lifestyle Reverse Cognitive Decline, Even in APOE4 Carriers
Coming from the “we knew this already” file (but we need to overwhelm them with the data) diet and lifestyle does indeed prevent and even reverse cognitive impairment. Including (importantly) in individuals with APOE4 and positive polygenic risk scores.
Evidence for the efficacy of diet and lifestyle interventions in preventing and reversing cognitive impairment, including among those with the APOE4 allele, is accumulating quickly. Bredesen, Toups et al., Sandison, and Ornish (in 2022, 2023, and 2024, respectively) all released papers examining intensive diet and lifestyle interventions for reversing cognitive impairment, with all showing significant benefits. Notably, Ornish published the first randomized controlled trial. I expect to see larger trials and (hopefully) more RCTs using these interventions in the near future. A 2024 paper on cardiorespiratory fitness and dementia prevention demonstrated a clear risk reduction, including in individuals genetically vulnerable to AD (as measured by polygenic risk scores for AD). Finally, research on omega-3 fatty acids—specifically DHA—showed that 2 grams per day for two years increased brain DHA levels, which were associated with better cognitive measures, particularly in APOE4 carriers. However, these benefits were only observed when DHA was used before symptom onset.
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