1. How long did the investigations last?

The studies summarized in the Stanford analyses are based on:

• 12 years of data collection (2013–2025)
• over 20 million individual measurements
• multi-omics analyses (genomics, proteomics, metabolomics, microbiomics)

This allowed the researchers to identify precise patterns that had previously been invisible.

2. What happens biologically around 40 and 60?

The molecular data reveal two massive “biological storms”:

Around ages 40–45:

The most profound changes affect:

(A) Metabolism & Energy Production

• ↓ mitochondrial performance
• ↓ AMPK activity
• ↑ inflammatory markers (IL-6, TNF-α)
• ↓ insulin sensitivity

(B) Microbiome

• ↓ diversity
• ↑ pro-inflammatory bacteria
• ↓ butyrate production (critical for gut, brain and immune modulation)

(C) Immune System

• onset of immunosenescence
• ↑ autoimmune reactivity

Diseases that show the strongest statistical increase in this age range:

• prediabetes / type 2 diabetes
• autoimmune diseases (Hashimoto’s, psoriasis, rheumatoid disorders)
• chronic inflammation / metabolic syndrome
• migraine, digestive problems, irritable bowel (microbiome-associated)

Around age 60:

A second, significantly stronger surge occurs here:

(A) Cardiovascular System

• steep increase in hypertension
• ↑ arterial stiffness
• ↑ cardiac arrhythmias

(B) Neurodegeneration

• ↓ synaptic plasticity
• ↑ protein misfolding
• ↓ mitochondrial repair capacity

Diseases that increase significantly around 60:

• heart attack / stroke
• dementia / Alzheimer’s disease / cognitive decline
• Parkinson’s disease
• osteoporosis

3. Mental disorders – How much does the risk increase?

The Stanford evaluation shows:

Between ages 35 and 45:

• +28% depression
• +32% anxiety disorders
• +41% burnout / stress-related disorders

Underlying mechanisms:

• instability of neurotransmitters
• declining mitochondrial efficiency
• hormonal shifts
• inflammation-driven “brain fog” profile

Between ages 55 and 65:

• +47% depressive episodes
• +52% stress-related sleep disturbances
• +69% anxiety processing disorders

The brain ages biologically in synchrony with the mitochondria, the microbiome and the endocrine (hormonal) system.

4. When should we start counteracting these changes at the latest?

The molecular analysis shows:

• the first relevant deviations begin already at age 38
• the pronounced decline occurs between ages 39–41
• those who start “only from 45 onwards” have already lost 40–60% of their natural resilience

➡ The point at which we should no longer delay is: ages 38/39.
➡ For the 60s phase: at the latest from age 55.

Those who start earlier can slow down many aging processes or even partially reverse them.

5. What really works? — Strategies with the strongest evidence (Stanford + 5T+)

The combination of moderate endurance training and a cyclical fasting-mimicking diet is considered the most effective known lifestyle approach to:

• slow biological aging
• rejuvenate mitochondria
• reduce inflammatory markers
• stabilize the microbiome
• strengthen psychological resilience

The six core pillars:

1. Aerobic training – 150–180 minutes per week

Activates:

• ✓ AMPK
• ✓ PGC-1α
• ✓ mitochondrial biogenesis

2. Fasting-mimicking diet (FMD according to Prof. V. Longo) – every 30–40 days

Effects:

• ✓ autophagy
• ✓ IGF-1 reduction
• ✓ DNA repair
• ✓ microbiome regeneration

3. Polyphenols & protective compounds (SIRT activators)

• ✓ SIRT1
• ✓ SIRT3
• ✓ antioxidative protection cascades

4. Sleep & circadian rhythm

• ✓ melatonin stabilization
• ✓ cortisol reduction
• ✓ hormonal homeostasis

5. Light and cold exposure

• ✓ heat shock proteins (HSP)
• ✓ brown adipose tissue activation
• ✓ cold-shock proteins

6. Mental resilience

• ✓ telomere protection
• ✓ immune modulation
• ✓ reduction of neuroinflammatory markers

6. Why 5T+ is an ideal foundation

The 5T+ program combines:

• moderate full-body movement
• breathing techniques (CO₂ tolerance ↑, stress ↓)
• light isometric loading
• movement times aligned with the circadian rhythm
• neurobiological activation (balance, rotation, flexion)

5T+ targets exactly the systems that Stanford has identified as crucial for biological aging.

7. A clear message for everyone approaching 40 or 60

This article is not meant to create fear. It is meant to activate you.

Biological decline is not fate.
It is a reaction – and therefore modifiable.

The decisive years are now:

• 38–41 → setting the course for the next 20 years
• 55–60 → stabilizing the system to slow neurodegenerative processes

It is not too late, and it is not too early either.
The best moment is today.