Longevity Medicine, NAD, and What You Can Do Right Now
Welcome back!
This newsletter is focused on longevity medicine. This topic is everywhere right now—on podcasts, in clinics, across social media, and increasingly in mainstream healthcare conversations. And while the interest is justified, the way longevity is often discussed feels oddly disconnected from how biology actually works.
Longevity medicine is not new. What’s new is our ability to measure, manipulate, and market it.
At its core, longevity medicine asks a simple question with an extraordinarily complex answer:
How do we preserve function, resilience, and quality of life as we age?
Not just how long we live… but how well.
🎧 New on The Trip Lab: #20 – NAD, Longevity, and the Line Between Promise and Proof
In the most recent episode of The Trip Lab, I use NAD as a lens to explore a broader issue in longevity medicine: the gap between mechanistic promise and clinical reality.
In the episode, we discuss:
Why NAD became such a central focus in longevity research
What raising NAD levels actually tells us—and what it doesn’t
Why improving a biomarker is not the same as improving health
How inflammation, insulin resistance, and lifestyle context shape whether NAD even matters
Why many longevity supplements work “on paper” but disappoint in practice
Rather than asking, “Does NAD work?” the episode reframes the question as: For whom, under what conditions, and toward what outcome?
The Biology Behind Longevity: The Hallmarks of Aging
Modern longevity science is largely organized around what are known as the Hallmarks of Aging, first described in a landmark 2013 paper and updated in 2023 to reflect advances in the field (López-Otín et al., 2013; López-Otín et al., 2023).
These hallmarks represent the core biological processes that drive aging across tissues and organ systems:
Genomic instability – Accumulation of DNA damage over time
Telomere attrition – Progressive shortening of chromosomal end caps
Epigenetic alterations – Changes in gene expression without changes in DNA sequence
Loss of proteostasis – Impaired protein folding and clearance
Deregulated nutrient sensing – Disruption of insulin, IGF-1, mTOR, and AMPK pathways
Mitochondrial dysfunction – Declines in cellular energy production
Cellular senescence – Accumulation of non-dividing, inflammatory cells
Stem cell exhaustion – Reduced regenerative capacity
Altered intercellular communication – Chronic inflammation (“inflammaging”)
The 2023 update expanded this framework to emphasize chronic inflammation, immune dysregulation, dysbiosis, and impaired autophagy as central drivers rather than downstream effects.
The key takeaway is this: Longevity is not a single-pathway problem. It is a systems-level phenomenon. Any intervention that claims to meaningfully alter aging by targeting one molecule or marker should be approached with skepticism.
What Longevity Medicine Is Actually Studying
Longevity medicine spans several overlapping research domains—many biologically compelling, even if their clinical translation is still evolving.
Cellular Energy & Mitochondrial Health
This includes NAD, sirtuins, and mitochondrial biogenesis. NAD is required for redox reactions, DNA repair, and metabolic signaling, and levels decline with age, inflammation, and metabolic disease (Verdin, 2015).
Nutrient-Sensing & Growth Pathways
mTOR, AMPK, and insulin/IGF-1 signaling determine whether cells prioritize growth or repair. Caloric restriction, protein modulation, and exercise influence these pathways and remain among the most reproducible lifespan-extending interventions in model organisms (Fontana & Partridge, 2015).
Inflammation, Immune Aging & Senescence
Chronic low-grade inflammation is now recognized as a central driver of aging-related disease across nearly every organ system (Franceschi et al., 2018). Senescent cells contribute to this inflammatory milieu, though senolytic therapies remain largely experimental in humans (Kirkland & Tchkonia, 2020).
Epigenetic Aging & Biological Age Clocks
DNA methylation clocks attempt to estimate “biological age,” but changing a clock score does not necessarily translate into improved health outcomes. These tools remain research-oriented rather than clinically directive (Jylhävä et al., 2017).
What You Can Do Right Now: Evidence-Based Longevity Foundations
If we strip away the hype, a striking truth remains: The most powerful longevity interventions are already available—and largely behavioral.
These are the interventions with the strongest and most consistent human data.
1. Physical Activity (Especially Resistance Training)
Exercise improves mitochondrial function, insulin sensitivity, immune regulation, and cognitive health. Resistance training preserves muscle mass and metabolic flexibility with aging (Holloszy, 2008; Phillips et al., 2017).
2. Metabolic Health Optimization
Insulin resistance accelerates nearly every hallmark of aging and predicts cardiovascular disease, dementia, and mortality independent of weight (DeFronzo & Ferrannini, 1991).
3. Sleep Quality
Sleep regulates immune signaling, glucose metabolism, and neurodegeneration. Chronic sleep deprivation increases all-cause mortality risk (Walker, 2017).
4. Stress Regulation & Nervous System Balance
Chronic psychological stress accelerates telomere shortening and promotes inflammation. Mind-body practices modulate autonomic balance and inflammatory pathways (Epel et al., 2004; Black & Slavich, 2016).
5. Social Connection & Purpose
Strong social ties predict longevity more robustly than many biomedical interventions. Social isolation carries a mortality risk comparable to smoking (Holt-Lunstad et al., 2015).
Closing Thoughts
Longevity medicine is not about outsmarting biology. It is about understanding it well enough to stop working against it.
The future of longevity will not be built on a single molecule or supplement. It will be built on systems thinking, humility, and a willingness to sit with uncertainty while the data mature.
My aim—both clinically and through Between Mind & Body—is to stay rooted in that middle space: curious, evidence-informed, and honest about what we know versus what we hope.