This is why Living Over 100 is Easier for Some - It's Not Just Luck

This is why some are Predisposed to Outlive Others, and how you can Tilt the Odds

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My Longevity Experiment
August 30, 2024

This is why Living Over 100 is Easier for Some - It's Not Just Luck

Longevity study how to live to 100, Live to 100

This is why some are Predisposed to Outlive Others, and how you can Tilt the Odds

Introduction

A recent study has uncovered that individuals who live beyond the age of 105 often possess a unique genetic makeup that enables their bodies to more effectively repair DNA. This discovery sheds light on the genetic factors contributing to extreme longevity and resistance to age-related diseases.

First-of-Its-Kind Study

For the first time, researchers have decoded the genomes of people with 'extreme longevity' in such detail. This groundbreaking study provides new insights into why these individuals live so long and are able to avoid many age-related diseases. It is widely understood that it is not the number of birthdays celebrated that leads to death, but rather the diseases associated with aging. Even deaths attributed to "old age" are ultimately caused by some form of biological failure.

Expert Insight

Paolo Garagnani, Associate Professor at the Department of Experimental, Diagnostic and Specialty Medicine at the University of Bologna, explained the study's approach: "Aging is a common risk factor for several chronic diseases and conditions. We chose to study the genetics of a group of people who lived beyond 105 years old and compare them with a group of younger adults from the same area in Italy, as people in this younger age group tend to avoid many age-related diseases and therefore represent the best example of healthy aging."

Study Outline

Garagnani and his colleagues recruited 81 semi-supercentenarians (individuals aged 105 years or older) and supercentenarians (individuals aged 110 years or older) from across Italy. The study was conducted in collaboration with several research groups in Italy and a research team led by Patrick Descombes at Nestlé Research in Switzerland. These participants were compared with 36 healthy individuals from the same region who had an average age of 68.

Blood Tests and Genetic Analysis

Blood samples were collected from all participants, and whole-genome sequencing was performed to identify genetic differences between the older and younger groups. The new genetic data was cross-referenced with results from a previously published study that analyzed 333 Italians aged over 100 and 358 individuals around the age of 60.

Key Findings

The researchers identified five common genetic changes that were more prevalent in the 105+/110+ age groups, located between two genes known as COA1 and STK17A. These genetic variants were also found in individuals aged over 100 when compared to published data. The computational analysis suggested that these genetic variations likely influence the expression of three different genes.

STK17A Gene

The most frequently observed genetic changes were linked to increased activity of the STK17A gene in certain tissues. This gene plays a crucial role in three key cellular health areas:

  • Coordinating the cell's response to DNA damage

  • Promoting apoptosis, or programmed cell death, in damaged cells

  • Regulating the levels of reactive oxygen species within cells

These processes are vital in preventing the onset and progression of many diseases, including cancer.

COA1 Gene

The genetic changes were also associated with reduced activity of the COA1 gene in some tissues. The COA1 gene is essential for proper communication between the cell nucleus and mitochondria, which are the energy-producing organelles in cells. Mitochondrial dysfunction is a significant factor in aging. Additionally, the same genomic region is linked to increased expression of the BLVRA gene in some tissues, which is crucial for cellular health due to its role in eliminating harmful reactive oxygen species.

Additional Expert Commentary

Cristina Giuliani, Senior Assistant Professor at the Laboratory of Molecular Anthropology, Department of Biological, Geological, and Environmental Sciences at the University of Bologna, commented on the study’s findings: “Previous studies showed that DNA repair is one of the mechanisms allowing an extended lifespan across species. We showed that this is true also within humans, and data suggest that the natural diversity in people reaching the last decades of life are, in part, linked to genetic variability that gives semi-supercentenarians the peculiar capability of efficiently managing cellular damage during their life course."

Mutation Analysis

The research team also examined the number of naturally occurring mutations accumulated by individuals in each group over their lifetimes. The findings revealed that those aged 105+ or 110+ had significantly fewer mutations in six out of seven genes tested. This lower mutation burden may have contributed to their resistance to age-related diseases, such as heart disease.

Study Significance

Massimo Delledonne, a full professor at the University of Verona, emphasized the study's uniqueness: "This study constitutes the first whole-genome sequencing of extreme longevity at high coverage that allowed us to look at both inherited and naturally occurring genetic changes in older people."

Conclusion

Claudio Franceschi, Professor Emeritus of Immunology at the University of Bologna, concluded: "Our results suggest that DNA repair mechanisms and a low burden of mutations in specific genes are two central mechanisms that have protected people who have reached extreme longevity from age-related diseases."

Final Thoughts

The role of NAD in DNA repair and its enhancement by NMN, an NAD booster, is noteworthy. The Italians in this study demonstrated a more effective DNA repair mechanism through the identified genetic variants. If NMN similarly enhances DNA repair and mitochondrial function in humans as it does in mice, it could be beneficial for those without such genetic advantages to support their DNA repair mechanisms proactively.

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