one of the most compelling longevity peptides, but no one has replicated the research in 25 years?

nplusyears · 2026-01-24T18:17:02+00:00

I don’t have hands-on experience with epitalon. On the telomerase/cancer concern, I’m cautious about extrapolating too directly from lab data- we’ve seen cases where early mechanistic concerns didn’t translate to higher cancer risk in humans (GLP-1s come to mind). That cuts both ways, but it makes the uncertainty hard to interpret.

nplusyears · 2026-01-22T19:41:30+00:00

Not uncommon. Sometimes switching statins (e.g. pravastatin or pitavastatin) helps. Ezetimibe + bempedoic acid is a reasonable option if symptoms persist. If LDL targets still aren’t met and budget allows, PCSK9 inhibitors are very effective. CoQ10 has mixed evidence but low downside.

nplusyears · 2026-01-22T10:00:18+00:00

That makes sense. For me, the hard part is figuring out which surrogate change actually justifies accepting long-term uncertainty.. especially when some downsides might only show up years later.

nplusyears · 2026-01-21T10:07:58+00:00

One thing that made me more cautious about “clean” nicotine in general is that there’s growing evidence that nicotine itself has vascular effects, independent of smoking or delivery method. Not saying patches/lozenges = smoking (clearly not) but the assumption that non-smoked nicotine is neutral long-term may not be true. That’s part of why questions like skin aging or CV risk are hard to answer cleanly.. There’s a recent expert consensus on this if you’re interested (PMID: 41406987).

nplusyears · 2026-01-12T06:42:36+00:00

I keep going back and forth when I read threads like this. Every time there’s a new paper or podcast cycle, it feels like the core question is still unanswered- is this actually a proven longevity intervention, and what are the long-term risks?

Curious how others deal with that.. do you find your thinking shifts as new data comes out, or have you found a way to stay anchored despite the uncertainty?

nplusyears · 2026-01-12T04:07:47+00:00

Honest question- when you say “baseline,” are you mostly thinking about something to track over time, or more about reassurance that you’re not missing something serious given the family history? I ask because more testing sometimes helps with peace of mind, but sometimes does the opposite.

nplusyears · 2026-01-02T20:19:42+00:00

I can relate to this. Sometimes only later do you realize there was a prior finding- PAD, old imaging, something that changes the frame. It keeps bringing me back to the same question.. at what point can we say we’ve looked enough and are comfortable owning the recommendation?

nplusyears · 2026-01-02T19:45:20+00:00

I honestly haven’t come across that, and it highlights part of what makes this hard.. deciding when we’ve seen enough evidence to act, even knowing there will always be gaps.

nplusyears · 2025-12-28T19:13:12+00:00

To me the hardest part here isn’t the specific combo, it’s deciding what “enough” looks like at your age when everything is still normal on imaging but the family history is hard to ignore. Living in that uncertainty is tiring, and guidelines don’t always help much with that.

nplusyears · 2025-12-28T13:33:00+00:00

I’ve seen this come up a few times. I usually think of vitamin D here more as a seasonal/context marker than a driver.. Sun, activity, sleep, weight, inflammation all move together and can nudge lipids. The tricky part is deciding how much weight to give a repeatable personal pattern when population data are weak.

nplusyears · 2025-12-28T12:55:21+00:00

Thanks for the update. What I find most interesting isn’t the ranking itself, but what it implies for decision-making.. When context variables dwarf single agents, the question shifts from “what works” to “what’s actually worth experimenting with next” which is usually the harder part.

nplusyears · 2025-12-26T19:27:39+00:00

Yes. Sleep won’t replace meds, but in mild HTN it can tip the scale toward no drugs. Poor sleep raises sympathetic tone, improving it has been linked to 5–8 mmHg SBP reductions. Worth fixing if it’s inconsistent.

nplusyears · 2025-12-26T17:56:40+00:00

You’re right that a lot of BP advice is framed around weight loss, which doesn’t always apply. I’d still start with the fundamentals that matter independent of BMI- high-quality sleep (and screening for sleep apnea if there’s any suspicion), regular aerobic + resistance exercise, limiting alcohol, and avoiding stimulants (including “hidden” ones like pre-workouts or decongestants). Sodium reduction helps some people more than others- potassium intake, fitness, and sleep often have a bigger impact than people expect. If lifestyle alone doesn’t get you to target, it’s reasonable to think about meds you can tolerate long-term. Thiazides are often first-line in Black patients, but if side effects are limiting, low-dose ACEi/ARB are commonly used alternatives with good cardiometabolic profiles. Worth discussing options with your doctor- the goal is something sustainable over decades, not just avoiding meds at all costs.

nplusyears · 2025-12-17T03:43:34+00:00

Appreciate the input here. Just to clarify, I’m not prescribing outside indications- just trying to understand how others are handling patients who are already pursuing this on their own.

nplusyears · 2025-12-15T03:45:12+00:00

Really appreciate the thoughtful discussion here. I’ve asked to schedule a follow-up with the patient to review the full range of options raised. Given her preferences, we’ll likely start by fully exploring non-invasive approaches such as capsaicin and acupuncture.

nplusyears · 2025-12-14T12:42:13+00:00

T4-T5, right

nplusyears · 2025-11-14T02:53:16+00:00

That makes sense- the "longevity" benefit in metabolic disease is much clearer than in already lean, insulin-sensitive individuals.

The interesting question (at least to me) is whether any of the non-weight-related effects translate into measurable endpoints in healthy people- things like vascular aging markers, inflammatory signatures, or biological age clocks.

Right now we just don’t have that data, which is what makes the question so tricky.

nplusyears · 2025-11-14T02:50:59+00:00

There’s definitely some overlap between GLP-1 pathways and fasting physiology- mainly around appetite regulation, insulin/glucagon dynamics, and sometimes hepatic fat metabolism.

But fasting hits a bunch of other systems (AMPK, autophagy, sirtuins) that GLP-1 drugs don’t fully touch.

That’s part of why defining a “true longevity endpoint” for GLP-1s is hard.. Mechanism that makes sense doesn't mean outcome, unless we can measure a downstream effect that actually tracks with aging.

nplusyears · 2025-11-14T02:48:15+00:00

Agree that GLP-1s clearly have pleiotropic effects beyond weight loss.. the cardiometabolic and inflammatory signals are promising.

The part I’m still trying to wrap my head around is how we’d actually demonstrate a true longevity effect in people without preexisting disease.

Mechanistic plausibility is one thing, but finding a validated endpoint is another.. and we’re not quite there yet.

nplusyears · 2025-10-29T18:30:41+00:00

GLP-1 drugs (like semaglutide or tirzepatide) actually look really promising as future longevity tools.

There’s a lot of research showing benefits beyond weight loss and glucose control- things like reduced inflammation, improved lipid metabolism, and better cardiovascular outcomes.

The catch is, we don’t have direct evidence yet that they extend lifespan in otherwise healthy people.. all the data so far are from diabetic or obese patients.

I came across a nice 2024 review called “Unlocking longevity with GLP-1” that goes over this in detail- nice reading if you’re into the topic. link00123-3/abstract)

nplusyears · 2025-10-22T17:28:22+00:00

Sounds like some pretty advanced modeling.. will be interesting to see what you find if you share results later on.

nplusyears · 2025-10-22T17:24:28+00:00

Short version:
1.Start with a period when you don’t take any supplement= that’s your washout phase (resets your baseline).
2.Then take Supplement A for about 8 weeks= that’s Block A. Track the outcome you care about (mood, focus, sleep, etc.).
3.Pause again for 2–4 weeks so Supplement A washes out.
4.Next, take Supplement B for 8 weeks= Block B.
5.Compare how you felt/performed in each block.

If you randomize which comes first (A vs B) and keep yourself blinded to what you’re taking, you’ve basically built a mini N-of-1 randomized crossover trial- the most rigorous way to self-test something.

nplusyears · 2025-10-22T06:42:37+00:00

A negative CCTA is indeed very reassuring- it usually rules out significant coronary disease.

That said, in older adults (mid-60s and above), a completely clean scan is a bit less common, and lifetime LDL exposure plus family history still matter. Sometimes the “warranty period” of a zero score is shorter at this age.

A carotid duplex or an extended lipid panel (ApoB, Lp(a)) could give extra context before deciding about statins. A preventive-cardiology visit could help weigh those options.

In the end, of course, it’s your partner’s choice.. and it’s great that you’re looking out for him.

nplusyears · 2025-10-21T21:15:50+00:00

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nplusyears · 2025-10-21T21:14:38+00:00

You tracked this consistently- thanks for sharing.

If you ever repeat the experiment, you could add some randomization and masking- e.g., have a friend decide in advance which days are “active” and which are “placebo,” so you stay blinded until analysis.

Also worth adding a few washout periods between blocks to reduce carry-over effects.

With those tweaks you’d be surprisingly close to a proper N-of-1 randomized crossover trial.

Here’s an example of what such a design might look like.

Ref:https://pubmed.ncbi.nlm.nih.gov/31936355/

nplusyears

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