Molecular Classes for Health and Longevity

Endogenous Longevity Molecules: The Body’s Internal Anti-Aging Network

Some of the most powerful longevity molecules aren’t supplements; they’re made by your own body. Aging happens when their production declines or their signaling becomes inefficient.

This page focuses on endogenous molecules that support energy production, vascular health, cellular repair, and long-term resilience.

Why Endogenous Molecules Matter for Longevity

These molecules:

  • Maintain mitochondrial energy production

  • Protect cells from oxidative and metabolic damage

  • Support circulation, cognition, and repair

  • Decline naturally with age, stress, and poor lifestyle inputs

Longevity is less about adding more and more about preserving what the body already knows how to make.

NAD⁺ (Nicotinamide Adenine Dinucleotide)

What it is: A central coenzyme required for energy production, DNA repair, and cellular survival.

Why it matters for aging:

  • Activates sirtuins (longevity-related enzymes)

  • Supports mitochondrial function

  • Declines significantly with age

Supported by: Exercise, fasting windows, niacin-rich foods (or precursors like NMN / NR)

Key studies:

  • Verdin, Science (2015)

  • Rajman et al., Cell Metabolism (2018)

Nitric Oxide (NO)

What it is: A gaseous signaling molecule that controls blood vessel dilation and circulation.

Why it matters for longevity:

  • Supports vascular and brain blood flow

  • Regulates blood pressure

  • Declines with endothelial aging

Supported by: Nitrate-rich vegetables (beets, arugula), exercise, oral microbiome health

Key studies:

  • Moncada & Higgs, New England Journal of Medicine (1993)

  • Lundberg et al., Nature Reviews Drug Discovery (2008)

Glutathione: The Master Antioxidant

What it is: The body’s primary intracellular antioxidant and detox molecule.

Why it matters:

  • Protects mitochondria and DNA

  • Supports immune defense and detoxification

  • Levels decline with aging and oxidative stress

Supported by: Sulfur-rich foods (broccoli, garlic), protein intake, sleep

Key studies:

  • Forman et al., Annual Review of Pharmacology and Toxicology (2009)

  • Ballatori et al., Toxicology and Applied Pharmacology (2009)

Choline

What it is: An essential nutrient and endogenous compound involved in cell membranes and neurotransmission.

Why it matters for brain aging:

  • Supports acetylcholine (memory and cognition)

  • Maintains cell membrane integrity

  • Important for liver and brain health

Top sources: Eggs, liver, fish, legumes

Key studies:

  • Zeisel & da Costa, Annual Review of Nutrition (2009)

  • Wallace & Fulgoni, Nutrients (2016)

Spermidine

What it is: A naturally occurring polyamine involved in cellular renewal.

Why it matters for longevity:

  • Activates autophagy (cellular recycling)

  • Associated with reduced mortality in human studies

  • Declines with age

Top sources: Wheat germ, legumes, aged cheese, mushrooms

Key studies:

  • Eisenberg et al., Nature Medicine (2016)

  • Madeo et al., Science (2018)

Key Takeaway

Longevity biology isn’t about biohacking extremes. It’s about supporting the molecules your body already relies on, consistently, gently, and intelligently.

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