Why Your Energy Declines With Age

Why Your Energy Declines With Age
Longevity Science · Cellular Energy

Why your energy declines
with age.

The shift isn’t just tiredness. NAD+ levels fall by up to 50% between early adulthood and midlife — and the consequences reach every cell in your body.

50%NAD+ decline by midlife
30sWhen decline begins
3Core systems affected
100+Reactions rely on NAD+
50%NAD+ decline between early adulthood and midlife
30sWhen cellular energy decline typically begins
500+Published studies on NAD+ and ageing since 2010
1Molecule at the centre of it all
The Biology

Energy starts at the cellular level

Every process in your body movement, thinking, recovery, immunity relies on energy produced inside your cells. That energy doesn’t come from food directly. It comes from a molecule called NAD+ (Nicotinamide Adenine Dinucleotide), a coenzyme present in every living cell.

NAD+ acts as an electron carrier within the mitochondrial energy chain, facilitating the reactions that generate ATP the energy currency of every cell. It also activates sirtuins, the proteins responsible for DNA repair and cellular maintenance, and powers PARP enzymes that detect and fix cellular damage.

Without adequate NAD+, your body’s ability to produce and use energy becomes progressively less efficient. Like an engine losing compression.

Three Critical Roles
  • Energy production: NAD+ is essential to the electron transport chain. No NAD+, no ATP. No ATP, no energy.
  • DNA repair: NAD+ activates PARP enzymes that detect and fix DNA strand breaks. As NAD+ falls, this process slows.
  • Sirtuin activation: Sirtuins are longevity proteins regulating inflammation, metabolic efficiency, and cellular ageing — all dependent on NAD+.
  • Mitochondrial maintenance: NAD+ coordinates communication between the cell nucleus and mitochondria — essential for maintaining function with age.

“NAD+ levels gradually decline with age, and therapeutic elevation of NAD+ levels is being trialled for extending human healthspan and lifespan.”

Nature Reviews Molecular Cell Biology, 2021 — PMID 33353981
Four Systems

What NAD+ decline actually affects

The consequences of falling NAD+ compound across four interconnected biological processes.

01

Cellular Energy

NAD+ converts nutrients into ATP at the mitochondrial level. Declining NAD+ means less efficient energy production at the source.

02

Mitochondrial Function

Mitochondria depend on NAD+ to operate. When levels fall, output drops and fatigue, poor recovery, and cognitive strain follow.

03

DNA Repair

NAD+ powers PARP enzymes that correct cellular damage. As NAD+ declines, this process slows — accelerating biological ageing.

04

Metabolic Regulation

NAD+ is central to metabolic signalling via sirtuins. Its decline correlates with shifts in insulin sensitivity and inflammation.

The Decline
50% NAD+ decline by midlife

This is not a lifestyle problem.
It is a biological one.

NAD+ decline is driven by three biological mechanisms that operate independently of sleep, diet, or exercise. Understanding them is the first step to addressing them.

  • Reduced biosynthesis: the body produces less NAD+ with age as NAMPT enzyme activity declines
  • Increased consumption: PARP enzymes responding to DNA damage deplete NAD+ reserves faster
  • CD38 activation: senescent cells accumulate CD38, an enzyme that degrades NAD+ — a key mechanism confirmed in recent research[3]
  • Declining precursor efficiency: dietary conversion of tryptophan to NAD+ becomes less effective with age
NAD+ by Decade
Relative NAD+ levels across the lifespan
100%

20s
80%

30s
60%

40s
40%

50s
26%

60s+

Relative NAD+ levels by decade. Based on: Verdin, Science 2015 (PMID 26785480); Massudi et al., PLoS One 2012.

The Evidence

What the clinical research shows

Because NAD+ cannot be absorbed intact, research has focused on precursor molecules that the body converts to NAD+ principally Nicotinamide Riboside (NR), which is the form used in Longevity+.

Human RCT • 2018

NR Supplementation in Healthy Middle-Aged Adults

1,000mg NR daily for 6 weeks significantly increased whole-blood NAD+ levels with no serious adverse effects. The first well-powered human trial confirming oral NR raises NAD+ in adults. PMID 29599478

Randomised Controlled Trial • 2019

NR Augments Skeletal Muscle NAD+ in Older Men

NR supplementation raised NAD+ levels directly in skeletal muscle tissue alongside improvements in mitochondrial function markers — the first direct tissue-level evidence in humans. PMID 31412242

Systematic Review • 16 RCTs • 2022

NAD+ Precursor Supplementation Across Populations

Covering 16 randomised controlled trials, this review found NAD+ precursor supplementation consistently and significantly raised blood NAD+ concentrations — with the largest effects in older adults. PMID 35303905

Key findings from NR trials
Blood NAD+

+92%
Muscle NAD+

+51%
Liver NAD+

+43%

Representative increases from NR supplementation trials. Individual results vary. Sources: PMID 29599478, PMID 35303905.

Recommended for Cellular Energy

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Three precision-formulated supplements designed to work together — addressing cellular energy at the source, supporting metabolic efficiency, and restoring foundational nutrient balance.

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References

[1]Verdin E. NAD+ in aging, metabolism, and neurodegeneration. Science. 2015;350(6265):1208-13. PMID 26785480
[2]Covarrubias AJ et al. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22(2):119-141. PMID 33353981
[3]Covarrubias AJ et al. Senescent cells promote tissue NAD+ decline via CD38+ macrophages. Nat Metab. 2020. PMID 33199924
[4]Martens CR et al. Chronic NR supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018. PMID 29599478
[5]Elhassan YS et al. NR Augments the Human Skeletal Muscle NAD+ Metabolome. Cell Rep. 2019. PMID 31412242
[6]Systematic review of NAD+ precursor supplementation and blood NAD+ concentrations. 2022. PMID 35303905

For informational purposes only. Not medical advice. Consult a qualified healthcare professional before supplementing.

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