The longevity industry is having a moment. Peptides, NAD infusions, senolytics, rapamycin, full-body MRIs, biological age tests, hormone optimization clinics. Most of this gets sold under the same banner: live longer, look younger, feel sharper. Your health is suppose to cost money. Spend more.
I am all for healthspan. That is the entire point of preventive medicine. But a meaningful portion of what is being sold as anti-aging is, at best, untested in humans, and at worst, biologically aligned with the very pathways that drive dysfunction.
In my previous post I laid out where I would start if I wanted to lower my cancer risk in my 30s, 40s, and 50s. This is the companion piece. What I would steer away from, even if a podcast host promises it adds five years to my life.
When I sort through the current longevity menu, I find two patterns. Some interventions deliver a real short-term benefit and quietly extract a long-term cost that is not on the label. Some interventions deliver a feeling that is not actually supported by human data while still carrying real risk.
A note before we get into it. I prescribe peptides. I use NAD precursors in specific cases. I order biological age testing when it is appropriate. My critique is about how these tools are being prescribed. To the wrong patients, by clinics with insufficient patient education and no monitoring, on evidence that does not yet exist. I am pro-evidence in humans, pro-monitoring, pro-asking the questions, pro-informed consent on experimental therapies and pro doing the unsexy, hard things.
Real benefit, real long-term cost
This is the most interesting category, because the short-term win is genuinely there. The trade-off is what gets quiet in the marketing.
TRT prescribed casually
In men with documented hypogonadism, testosterone replacement reliably improves libido, body composition, and mood. The TRAVERSE trial confirmed cardiovascular safety in that population. The clinical use case is real.
The longevity clinic version is not the same medicine. A symptom checklist, a single morning testosterone level, no SHBG, no estradiol, no PSA, no hematocrit, no fertility conversation, and a script. Patients walk out with prescriptions for a therapy whose long-term costs include testicular atrophy, suppressed fertility that is often not reversible after years on therapy, polycythemia that requires monitoring or dose adjustment, with the pulmonary embolism signal seen in TRAVERSE, sleep apnea worsening, and dependency.
The reality is that I have sat across from many men in their 30s and 40s who were not properly counseled about fertility before starting TRT and are now struggling to conceive with their partners.
Most men presenting with fatigue, low libido, and brain fog have a metabolic, sleep, or stress problem first. Yes, TRT will mask those problems for a while. But the original problem keeps progressing in the background. Sleep apnea continues to damage cardiovascular and metabolic health. Insulin resistance keeps advancing. TRT will improve some of these markers, the patient feels better, and stops asking why he felt bad in the first place. Five years later, the underlying disease has compounded and the TRT can no longer paper over it. Many men end up needing more testosterone.
GLP-1s as longevity drugs
The short-term win here is unambiguous and well-documented. Semaglutide and tirzepatide produce real weight loss, real glucose control, real lipid improvements, and real cardiovascular benefit in the populations they were trialed in. SELECT, STEP, and SURMOUNT are not small studies. The data is the data.
The longevity application is a different question. Microdoses prescribed off-label in metabolically healthy adults have not been studied for long-term safety in that population. The safety profile we know is in patients who needed the drug.
The bigger trade-off is body composition. GLP-1 weight loss is not all fat. Significant lean mass loss is well documented in the trials and visible in clinic. In a 45-year-old who is not actively resistance training and eating high protein, the loss of muscle mass over months to years is the opposite of what longevity should be doing. Sarcopenia is one of the most underappreciated predictors of poor outcomes in cancer treatment, surgical recovery, and falls in your 70s. Losing muscle in your 40s for cosmetic reasons is borrowing from your eighth decade.
If a patient has obesity, prediabetes, or metabolic syndrome that has not responded to first-line lifestyle work, GLP-1s are reasonable medicine. If they are looking lean and want to look leaner, my answer is no.
High-dose protein and the leucine arms race
Adequate protein in older adults is essential. The short-term effects on muscle protein synthesis and body composition are well-established. I am not pulling protein out of anyone’s diet.
The longevity world often treats protein optimization as if more is always better. Chronically very high protein intake, particularly from animal sources rich in branched-chain amino acids, sustains mTOR activation. mTOR is part of how we build and preserve muscle. It is also part of how cells proliferate when we do not want them to. The cleanest longevity epidemiology, including Adventist cohorts and other Blue Zone-style populations, tends to support moderate protein intake with a stronger plant emphasis for lower cancer risk and overall mortality.
The other long-term cost is opportunity. People prioritizing protein bars, shakes, and meat-heavy meals are often displacing the thing most consistently associated with better long-term outcomes: fiber. Fiber is not just about bowel regularity. It shapes the microbiome, improves insulin sensitivity, lowers LDL cholesterol, supports estrogen metabolism, increases short-chain fatty acid production, and is consistently associated with lower cardiovascular disease, colorectal cancer, and all-cause mortality risk. Most Americans are profoundly under-consuming it.
The irony is that many people chasing “optimal” longevity macros are eating less than 20 grams of fiber daily while meticulously tracking leucine thresholds. Meanwhile, some of the strongest nutrition longevity data we have repeatedly points back toward minimally processed plant foods, legumes, vegetables, intact grains, nuts, seeds, and overall dietary diversity.
The clinical version. Get enough protein to build and maintain muscle, generally around 1.2 to 1.6 g/kg of ideal body weight for most adults, often higher for older adults, cancer patients, and those actively training. Get it from whole, lean sources: fish, eggs, poultry, legumes, fermented soy foods, dairy if tolerated, and moderate amounts of less-processed red meat. Build meals around plants first, not around protein products. Aim for fiber intake that actually reaches physiologic relevance, often 30 to 50+ grams daily from real food.
Whole foods carry micronutrients, polyphenols, fermentation substrates, and satiety signaling that isolated protein strips out. Powders, bars, and isolates have a role for genuine logistical gaps, not as the dietary foundation. Periodize. Cycle higher and lower intake days. Train enough to justify the extra protein.
GH secretagogue peptides
Tesamorelin is FDA-approved for HIV-associated visceral adiposity and produces measurable reductions in visceral adipose tissue. The short-term effect on a defined endpoint is real. Sermorelin, ipamorelin, and CJC-1295 also raise IGF-1 measurably, and many patients report improved sleep and recovery in the early months.
The long-term cost is the IGF-1 story. The IGF-1 axis is one of the most well-characterized proliferative signals in human biology. Acromegaly, where GH and IGF-1 are chronically elevated, is associated with higher rates of colorectal cancer, cardiovascular disease, and connective tissue overgrowth. We do not have human data on what years of supraphysiologic GH stimulation does in people who started with normal levels.
There is also the dependency issue. Patients who stay on these compounds for a year or two often struggle when they try to stop. The hypothalamic-pituitary feedback loop adapts, endogenous signaling downregulates, and many end up feeling worse coming off than they did before they started.
I prescribe peptides selectively, for short and clearly defined clinical situations. I do not view them as casual longevity add-ons. Longevity is not about shortcuts. It is about respecting biology over decades. The recovery, body composition, and performance gains patients feel today may come with physiologic consequences we cannot yet fully see, especially when these pathways are chronically manipulated in healthy individuals without a real discussion of tradeoffs.
The short-term claim itself does not hold up
This is the category the longevity industry would rather you not look at too closely. The marketing implies a robust short-term effect. The human data does not.
NAD IV infusions and most NAD precursors
NMN and NR raise blood NAD. That much is well-established. Whether the biomarker change translates to functional or subjective benefit in healthy adults is far less clear. The trials are small, short, and inconsistent. Some show modest insulin sensitivity improvements. Some show nothing.
NAD IV infusions, the version sold at $400 to $600 a session, have no controlled efficacy data despite the marketing. The “feel sharper” claim is anecdotal. I have experimented on myself. Did I feel different? Maybe. Which could entirely be chalked up to the placebo plus the saline volume itself.
There is also a mechanistic problem worth naming. NAD does not readily cross cell membranes. IV NAD is broken down to nicotinamide and other precursors before cellular uptake, which means the biological endpoint of an IV may not be meaningfully different from oral NR, despite the price and the theater.
The biology gives one more reason for caution. NAMPT, the rate-limiting enzyme in the NAD salvage pathway, is upregulated in many cancers and supports tumor metabolism. Active oncology research is targeting NAMPT inhibition as anti-cancer therapy, which sits in tension with chronically loading the system in someone who may have undiagnosed disease. This remains controversial and far from settled. Many integrative providers routinely use IV NAD and NAD precursors in cancer patients and report doing so without apparent harm. We do not yet have strong long-term human outcome data to confidently define the risk-benefit profile in oncology.
BPC-157 and TB-500
These get bundled into peptide stacks for “recovery” and “gut healing.” There are essentially no controlled human trials for either. The animal data shows angiogenic effects, which is a property tumors require to grow. The subjective improvements patients report are anecdotal in a population already paying thousands for the protocol, which is the definition of a setting where placebo effects dominate.
What to focus on instead. For tissue recovery, the practical tools are not exotic. Sleep is the biggest lever. Adequate protein at meals supports remodeling. Collagen peptides 15 g with vitamin C taken 30 to 60 minutes before targeted tendon or ligament work improves tissue collagen synthesis (Shaw, Baar lab). Creatine has decades of human safety and efficacy data, with emerging signals for connective tissue and brain. Omega-3s, curcumin, and tart cherry have modest data for post-exercise soreness and inflammation. Sauna has cardiovascular and recovery data that BPC-157 does not.
For gut work, start by removing what injures it. NSAIDs, alcohol, ultra-processed food, sleep deprivation, and unmanaged stress drive most of what people are trying to heal with peptides. From there:
Zinc carnosine 75 mg twice daily for mucosal repair, particularly NSAID-induced damage
L-glutamine 5 g once or twice daily for enterocyte support
DGL (deglycyrrhizinated licorice) for upper GI mucosal protection
Slippery elm or marshmallow root for mucilaginous coating
Saccharomyces boulardii during and after antibiotics
Strain-specific probiotics matched to the indication, not generic blends
Polyphenol-rich foods (berries, green tea, olive oil) for microbial diversity
The boring version is more likely to actually work than a peptide stack.
I have absolutely met patients who have tried everything, done the work consistently, and still feel stuck with no meaningful movement despite addressing the fundamentals. In select cases like that, I think it is reasonable to consider peptides thoughtfully and cautiously as a tool, not a shortcut.
At-home senolytic protocols
Fisetin and the dasatinib-plus-quercetin combination are still primarily supported by animal data and a handful of short-term human trials in narrow populations. The doses promoted on podcasts and social media are not the doses used in the human work that does exist.
Reported benefits like less inflammation, better recovery, and less joint stiffness are subjective and uncontrolled. People may genuinely feel something. That is not the same as established clinical benefit.
The strongest caution applies to dasatinib. It is a prescription tyrosine kinase inhibitor used in oncology, with known risks including pleural effusions, cytopenias, immunosuppression, and cardiac toxicity. Casual self-directed use in longevity protocols deserves more caution than it currently gets.
There is also a tendency to frame senescent cells as universally harmful. They contribute to aging and chronic disease, and they also play roles in wound healing and tissue repair. Clearing them indiscriminately may not be biologically neutral.
Off-label rapamycin for healthy aging
Most patients feel nothing in particular on rapamycin, which is the honest read. The short-term subjective benefit is essentially absent. The case for it rests entirely on extrapolation from animal lifespan data.
The long-term human safety in healthy adults is also essentially absent. We know rapamycin’s profile in transplant patients and in tuberous sclerosis. Possible side effects include glucose dysregulation, lipid elevation, mucositis, impaired wound healing, and infection susceptibility. Lower intermittent dosing for longevity may have a different profile, but in practice I have seen even low-dose rapamycin worsen blood glucose and lipid profiles.
What to focus on instead. The pathways rapamycin is meant to modulate, mTOR inhibition and autophagy induction, are also accessible through inputs with far better human evidence.
Caloric restriction has the strongest data. The CALERIE trial of 25 percent caloric restriction over two years showed improved metabolic flexibility, lower inflammatory markers, and slowed biological aging on the DunedinPACE clock. Fasting-mimicking diet protocols (Longo) lower IGF-1 and glucose markers in human trials. Time-restricted eating with a 10 to 12 hour window produces modest mTOR cycling and autophagy activation with metabolic benefit. Start the eating window earlier rather than later. Eat breakfast like a king, lunch like a prince, and dinner like a pauper.
Exercise activates AMPK and induces autophagy directly. Endurance training drives the AMPK side. Resistance training builds the metabolic and physical reserve that rapamycin cannot. Both have human outcome data that rapamycin does not.
Sleep! Autophagy is heavily circadian. Disrupted sleep blunts the same housekeeping rapamycin is supposed to upregulate.
Dietary spermidine, found in wheat germ, aged cheese, mushrooms, legumes, and whole grains, is associated with reduced all-cause mortality in observational cohorts (Kiechl 2018). Polyphenols like EGCG, curcumin, and resveratrol activate AMPK and SIRT1 pathways with varying levels of human data.
What actually compounds in your favor
The pattern across all of the above is that the interventions sold hardest in the longevity space are often the ones with the weakest data. The interventions that compound in your favor have a different shape. They do not feel dramatic in the first week or even month. They quietly accrue benefit over years.
Sleep on a consistent schedule. Resistance training to build and maintain muscle. Aerobic capacity that protects mitochondria and immune surveillance. Adequate but not excessive protein from whole foods. Fiber from diverse plants, north of 30 grams a day. Metabolic health with fasting insulin under 6 and ApoB optimized. Vitamin D in range. Reduced alcohol. Reduced exposure to endocrine disruptors. Functional labs to find deficiencies and over-accumulation, then fix them. Periodic prolonged fasts of 24 to 72 hours, one to four times a year if appropriate for you. Strong relationships. Time outdoors. Sunlight in the morning. Stress regulation that you actually practice rather than buy.
Let the body do the housekeeping it already knows how to do.
Boring? Yes. That is the point.
How I think about it
When a patient brings me a longevity protocol, I ask the same questions. What else are you doing as far as diet and lifestyle modifications? Are you aware of the long-term effects of the protocol you are on? What will it look like to come off it?
If you want to add something investigational on top of a strong foundation, I am not opposed, as long as you are doing it with full information, real monitoring, and honest acknowledgment that you are running a single-patient trial on yourself. What I see going wrong is people skipping the foundation and stacking new molecules on top of bad sleep, alcohol, and unmanaged stress.
I hate to sound like a broken record, but healing is practice. Not something you buy in a bottle.
The point of all of this is to live a life that is well-lived for as long as it is well-lived. Love. Connection. Community. Time in nature. Mistakes and imperfections along the way. That part has not changed since the last post and it is not going to.
I am keeping an open mind on every one of these molecules and protocols as the human data comes in. Several will probably earn a place. Several will not. I am not in a rush to find out which is which on my own body, or on yours.
Most of what is being sold to you in this space is wearing grandma’s bonnet. The teeth are still teeth. Ask the question early enough to matter.
Ksenia Malarkey, ND is a naturopathic physician specializing in integrative oncology, hormones, and metabolic health.
She provides medical care for Washington residents and offers global health coaching.
To schedule a free 15-minute consult, visit drkseniamalarkey.com
This is so important in today’s flood of social media information. I often hear cancer patients being advised by “friends” to take supplements or peptides for longevity and “cell boosting,” without realizing the same logic does not necessarily apply in cancer. Glad you’re highlighting this because it’s a complex field that gets heavily oversimplified online, despite the potential risks involved. Another reason I focus on this myself in cancer context.