Not a specific ‘aging gene’, but the length of a gene determines aging

Not a specific ‘aging gene’, but the length of a gene determines aging
Not a specific ‘aging gene’, but the length of a gene determines aging

As we get older, our cells are less likely to express longer genes, the scientists write in an opinion article. According to them, aging may have less to do with specific “aging genes”, but more to do with the length of a gene.

A decrease in the expression of long genes with age occurs in a wide range of animals, from worms to humans, in various human cell and tissue types, and also in patients with neurodegenerative diseases. Mouse experiments show that the phenomenon can be reduced with known anti-aging therapies, including dietary restrictions.

Aging genes never found

Hoeijmakers: ‘Aging is accompanied by changes at molecular, cellular and organ level: from altered protein production to suboptimal cell metabolism to compromised tissue architecture. We thought that these changes result from DNA damage due to exposure to harmful substances such as UV radiation or reactive oxygen species that are released during our own metabolism.’

Much research has focused on specific genes that can speed up or slow down aging, but no such ‘aging genes’ have ever been found. Hoeijmakers: ‘Instead, susceptibility to aging seems to be related to the length of the genes. Our explanation is that aging is much more random than specific genes. It is a physical phenomenon related to the length of the genes.’

Long genes simply have more potential places to become damaged

According to the researchers, the explanation for this is relatively simple: long genes simply have more potential places that can become damaged. The researchers compare it to a road trip: the longer the journey, the more likely something will go wrong along the way. Hoeijmakers: ‘And because some cell types express more longer genes than others, there is a greater chance that these cells will be less able to do their work as they get older.’

Cells that do not divide or divide very rarely also appear to be more susceptible compared to rapidly dividing cells. After all, long-lived cells have more time to build up DNA damage and must rely on DNA repair mechanisms to repair the damage, while rapidly dividing cells generally have a shorter lifespan.

Nerve cells extra susceptible

Nerve cells are particularly susceptible to aging because they express particularly long genes and divide slowly or do not divide at all. Hoeijmakers emphasizes the link between aging and neurodegeneration: ‘Many of the long genes in the brains of Alzheimer’s patients no longer function properly, disrupting processes in the cell, resulting in protein clumping. And children with cancer, who are cured by DNA-damaging chemotherapy, also later suffer from premature aging and neurodegeneration.’

The link between the decline in the expression of long genes and aging is strong, but a causal relationship has not yet been demonstrated. Hoeijmakers: ‘Of course you never know which came first, the egg or the chicken, but we see a strong relationship between this phenomenon and many of the known characteristics of aging.’

In future studies, the researchers want to further study the mechanism of the phenomenon and its evolutionary implications and better map the relationship with neurodegeneration.

The article is in Dutch

Tags: specific aging gene length gene determines aging


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