Jet lag is not tiredness. It is a genuine physiological desynchronisation between your internal biological clock and the time zone you've landed in. Your circadian rhythm — the 24-hour molecular clock that governs sleep, waking, hormone release, digestion, body temperature and cognitive performance — is anchored to your departure time zone. Cross three or more time zones rapidly and every internal process runs on the wrong schedule. The result is poor sleep, daytime fatigue, reduced cognitive sharpness, irritability and digestive disruption — all at once.

What most people don't know is that their circadian clock is partly regulated by NAD+. The clock genes CLOCK and BMAL1 are directly controlled by SIRT1 — a sirtuin protein that requires NAD+ to function. When NAD+ is adequate, SIRT1 runs efficiently, the molecular clock ticks precisely, and the body can re-entrain to a new time zone relatively quickly. When NAD+ is depleted — as it is in most people over 40, whose levels have been declining for years — SIRT1 activity falls, the clock loses precision, and re-entrainment slows.

This is the direct biological reason jet lag gets worse with age. It is not imagination. It is a measurable decline in the NAD+/SIRT1 system that powers circadian precision.

A commercial aircraft cabin is pressurised to the equivalent of 6,000–8,000 feet altitude — not sea level. At that pressure, blood oxygen saturation drops slightly but measurably. Your cells compensate, but compensation costs energy. Every mitochondrion in your body is working fractionally harder to maintain normal function for 8–14 hours. Add cabin humidity below 20% — drier than most deserts — and you can lose over a litre of fluid without feeling obviously thirsty. Dehydration directly impairs mitochondrial efficiency.

Simultaneously, the physical stress of immobility, recirculated air, immune activation from proximity to other travellers, and the disrupted sleep most people manage on long-haul flights all activate PARP enzymes — the cellular repair proteins that consume NAD+ when they run. A 12-hour flight is, from a cellular perspective, a sustained NAD+-depleting event.

The hollowed-out feeling on arrival is not weakness. It is cellular metabolism depletion after hours of mitochondrial stress.

Most people going somewhere sunny have sunscreen on their packing list. Very few have thought about what UV radiation does at the cellular level — and why NAD+ is directly involved in the skin's response to it.

When UV radiation hits skin cells, it causes DNA damage — specifically the formation of cyclobutane pyrimidine dimers and oxidative lesions. Your skin has repair systems for this, but they are energy-dependent and NAD+-hungry. The primary repair enzyme, PARP-1, consumes large quantities of NAD+ when it activates in response to UV damage. Research published in the Journal of Photochemistry and Photobiology demonstrated this precisely: UV triggers PARP activation, PARP consumes NAD+, and when NAD+ runs out, skin cells lose the ability to properly repair and renew themselves. The long-term result is photoageing — fine lines, elasticity loss, uneven tone.

A 2025 study comparing NAD+ precursors in UV-damaged human skin fibroblasts found NMN outperformed every other NAD+ precursor tested. NMN reduced cellular ageing markers by 30%, restored expression of the collagen genes COL1A1 and COL3A1 that UV exposure suppresses, and activated sirtuin repair proteins SIRT5 and SIRT6. The protective effect persisted for over 10 days.

Airports and aircraft cabins are among the most immunologically challenging environments most people regularly occupy. Recirculated air, high passenger density, hard surfaces, and the physiological stress of disrupted sleep and circadian rhythm all create conditions that put your immune system under pressure precisely when it needs to be working well.

NAD+ is required for every immune cell — T cells, B cells, natural killer cells, macrophages — to function. It is also consumed rapidly during immune activation via the same PARP mechanism that UV and flight stress trigger. Research published in Trends in Immunology confirmed that viral infections deplete cellular NAD+ through PARP activation, and that NAD+ precursors may help maintain immune capacity during challenge.

Travel also disrupts gut health — different food, different water, different microbial environments, often reduced dietary variety. Since roughly 70% of your immune system is gut-associated, this matters more than people realise. The disrupted sleep and circadian desynchronisation of jet lag independently suppress immune function — sleep-deprived immune cells are measurably less effective at every stage of the immune response.

Most people sleep worse in unfamiliar environments, on different beds, with different noise and light patterns. Add a 5–8 hour time zone shift and the challenge becomes significant. Poor sleep on holiday is not just unpleasant — it impairs every other system we've discussed. Immune function, cellular repair, cognitive performance and energy all depend on adequate sleep to reset.

NAD+ regulates the circadian clock genes that govern sleep-wake cycles. Lower NAD+ means a less precise circadian signal, which means it takes longer to fall asleep, recovery and overnight routine is lighter, and waking at the appropriate local time is harder. A 2024 randomised, double-blind, placebo-controlled trial confirmed that NMN supplementation significantly improved recovery and overnight routine after 12 weeks, including reductions in daytime dysfunction and global sleep impairment.

Magnesium supports a separate but complementary pathway — the GABAergic system that promotes sleep onset and reduces anxiety-driven wakefulness. Magnesium glycinate is the most bioavailable form and is gentle enough to use every night without dependency.

A good holiday should refuel you, not deplete you. The frustrating reality for many people — particularly those in their 40s and beyond — is that they return from two weeks in the sun feeling only marginally better rested than when they left. The cellular metabolism deficit they arrived with is too deep for two weeks of better overnight recovery and sunshine to fully address.

This is the clearest argument for consistent NMN supplementation in the weeks before a holiday rather than just during it. A 2024 randomised controlled trial found NMN significantly improved physical performance and quality of life scores at all doses tested. A separate 2024 trial specifically found NMN reduced afternoon fatigue — the mid-holiday energy dip that many people on busy itineraries recognise immediately.

Cellular metabolism is not rebuilt overnight. The mitochondrial efficiency that NAD+ supports improves cumulatively over weeks of consistent supplementation. Starting NMN the morning you land is better than not starting at all — but the person who has been taking it consistently for eight weeks before they travel will feel the difference from day one.