People Aged Over 105 may Have More Efficient DNA Repair

Whole-genome sequencing of people who live beyond 105 and 110 years reveals unique genetic signatures linked to protective processes such as DNA repair.

People aged above 105 years may have a genetic background with more efficient DNA repair, according to a study published in eLife.

These people have had their genomes decoded in a detailed manner first time, providing clues as to why they live so long.br>
"Aging is a common risk factor for several chronic diseases and conditions," explains Paolo Garagnani, Associate Professor at the Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy, and a first author of the study.

‘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.’
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"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."

The study involved 81 semi-supercentenarians and supercentenarians from across the Italian peninsula. They were compared with 36 healthy people from the same region who were 68 years old.

Blood samples were collected from all the participants and conducted whole-genome sequencing to look for differences in the genes between the older and younger group.

Telomere Shortening And Ageing
Telomeres are cap- like structures at chromosome ends that play an important role in ageing and in the initiation and progression of various diseases.

They then cross-checked their new results with genetic data from another previously published study which analyzed 333 Italian people aged over 100 years old and 358 people aged around 60 years old.

Five common genetic changes were seen in COA1 and STK17A. Data collected from computational analyses predicted that this genetic variability likely modulates the expression of three different genes.

Increased activity of the STK17A gene in some tissues helps in coordinating the cell's response to DNA damage, encouraging damaged cells to undergo programmed cell death and managing the amount of dangerous reactive oxygen species within a cell. These processes are involved in the growth of cancer.

Genetic changes are also linked to reduced activity of the COA1 gene in some tissues. This gene is known to be important for the proper crosstalk between the cell nucleus and mitochondria - the energy-production factories in our cells whose dysfunction is a key factor in aging.

The same region of the genome is linked to an increased expression of BLVRA in some tissues - a gene that is important to the health of cells due to its role in eliminating dangerous reactive oxygen species.

"Previous studies showed that DNA repair is one of the mechanisms allowing an extended lifespan across species," says Cristina Giuliani, Senior Assistant Professor at the Laboratory of Molecular Anthropology, Department of Biological, Geological and Environmental Sciences, University of Bologna, and a senior author of the study.

"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."

People aged 105+ or 110+ had a much lower burden of mutations in six out of seven genes tested.

"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," says Massimo Delledonne, Full Professor at the University of Verona and a first author of the study.

"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," concludes senior author Claudio Franceschi, Professor Emeritus of Immunology at the University of Bologna.

Source-Medindia