Aging may be less about specific "aging genes" and more about how long a gene is. Many of the changes associated with aging could be occurring due to decreased expression of long genes, say researchers in an opinion piece publishing March 21 in the journal Trends in Genetics. Aging is associated with changes at the molecular, cellular, and organ level -- from altered protein production to sub-optimal cell metabolism to compromised tissue architecture. These changes are thought to originate from DNA damage resulting from cumulative exposure to harmful agents such as UV radiation or reactive oxygen species generated by our own metabolism. For a long time, the aging field has been focused on genes associated with aging, but our explanation is that it is much more random -- it's a physical phenomenon related to the length of the genes and not to the specific genes involved or the function of those genes

 

It essentially comes down to chance; long genes simply have more potential sites that could be damaged. The researchers compare it to a road trip -- the longer the trip, the more likely that something will go wrong. And because some cell types tend to express long genes more than others, these cells are more likely to accumulate DNA damage as they age. Cells that don't (or very rarely) divide also seem to be more susceptible compared to rapidly replicating cells because long-lived cells have more time to accumulate DNA damage and must rely on DNA repair mechanisms to fix them, whereas rapidly dividing cells tend to be short-lived. Because neural cells are known to express particularly long genes and are also slow or non-dividing, they are especially susceptible to the phenomenon, and the researchers highlight the link between aging and neurodegeneration.

 

It is speculated that damage to long genes could explain most of the features of aging because it is associated with known aging accelerants and because it can be mitigated with known anti-aging therapies, such as dietary restriction (which has been shown to limit DNA damage). Many different things that are known to affect aging seem to lead to this length-dependent regulation, for example, different types of irradiation, smoking, alcohol, diet, and oxidative stress. However, although the association between the decline in long-gene expression and aging is strong, causative evidence remains to be demonstrated. In future studies, the researchers plan to further investigate the phenomenon's mechanism and evolutionary implications and to explore its relationship with neurodegeneration.