Legends tell of figures with extraordinary longevity—Peng Zu (said to live 800 years), Zhang Sanfeng (over 200 years), and the "Young Marshal" of Northeast China (100 years). But what is the actual limit of human lifespan?
In May 2021, an international research team used the Dynamic Organism State Index (DOSI) to simulate the entire human aging process. They concluded that the maximum human lifespan ranges from 120 to 150 years.
With global population aging worsening, diet and metabolism are key to regulating human lifespan. Scientists are now exploring interventions to improve the health and longevity of the elderly.
Figure Note: Experimental simulation of maximum lifespan (X-axis: Age in years; Y-axis: DOSI or related activity metrics).
Key Research Findings: SIRT6 Protein—The "Anti-Aging Powerhouse"
On May 28, 2021, Dr. Cohen’s team from Bar-Ilan University published a study in Nature Communications. They found that increasing SIRT6 protein levels extends the lifespan of mice by approximately 27%. Additionally, SIRT6 optimizes energy balance in the liver and adipose tissue, reducing frailty and prolonging lifespan.
1. What Are Sirtuins Proteins?
Sirtuins are a family of proteins that require NAD+ (nicotinamide adenine dinucleotide) to function. When the body has sufficient NAD+, Sirtuins play a crucial role in maintaining DNA health and cellular metabolism.
Among Sirtuins, two proteins—SIRT1 and SIRT6—actively regulate metabolism and delay aging. The most effective way to supplement NAD+ is by taking NMN (nicotinamide mononucleotide).
2. Increasing SIRT6 Levels Extends Lifespan
The research team genetically modified mice into three groups:
- Mice with increased SIRT1 production
- Mice with increased SIRT6 production
- Mice with increased production of both SIRT1 + SIRT6
After a 40-month experiment (a full lifespan for mice), the results showed:
- The average lifespan of SIRT6-transgenic mice was ~27% longer than that of normal (wild-type, WT) mice.
- SIRT6-transgenic mice lived ~15% longer than SIRT1-transgenic mice.
- There was no significant difference in lifespan between SIRT6-transgenic mice and SIRT1 + SIRT6-transgenic mice—confirming that SIRT6 plays a more critical role in extending lifespan.
3. Increasing SIRT6 Reduces Frailty
The team also compared the running distance of aged transgenic mice on a spinning wheel. The results revealed:
- At 15 months of age (elderly for mice), SIRT6-transgenic mice and SIRT1 + SIRT6-transgenic mice ran the farthest.
- SIRT1-transgenic mice and normal mice showed significantly lower stamina.
This indicates that increasing SIRT6 protein levels reduces frailty in aged mice and improves their physical strength.
4. SIRT6 Boosts NAD+ to Enhance Energy Production
During aging, the metabolic process that generates energy (ATP) in the liver gradually deteriorates, leading to energy imbalance in the body.
Stimulating SIRT6 production:
- Increases NAD+ levels.
- Activates the tricarboxylic acid (TCA) cycle.
- Promotes energy production in liver cells.
- Delays cellular senescence.
Additionally, increasing SIRT6 levels triggers physiological responses that prompt the body to burn fat for energy—similar to the effects of intermittent fasting. This serves as a calorie-restriction-like method to extend lifespan.
Research Significance & Outlook
Dr. Cohen’s lab is currently developing methods to maintain health and extend lifespan by targeting the SIRT6 protein. If SIRT6 can be activated in humans, it could effectively extend lifespan—potentially making "four-generation families" a common phenomenon and having a profound impact on human health and longevity.
Additional Reading
For more information on the link between Sirtuins proteins and NAD+:
- "NAD+ Directly Improves Hepatocyte Regeneration, Promotes Metabolism, and Delays Aging"
References
Roichman, A., Elhanati, S., Aon, M. A., Abramovich, I., Di Francesco, A., Shahar, Y., Avivi, M. Y., Shurgi, M., Rubinstein, A., Wiesner, Y., Shuchami, A., Petrover, Z., Lebenthal-Loinger, I., Yaron, O., Lyashkov, A., Ubaida-Mohien, C., Kanfi, Y., Lerrer, B., Fernández-Marcos, P. J., Serrano, M., Gottlieb, E., de Cabo, R., Cohen, H. Y. (2021). Restoration of energy homeostasis by SIRT6 extends healthy lifespan. Nature Communications, 12(1): 3208. https://doi.org/10.1038/s41467-021-23545-7.