Aging is a very complex degenerative process whereby the cellular homeostasis of an organism begins to break down in an environment of increasing degradation and decline. It’s also a primary risk factor for a variety of diseases and disorders. This is not a process that begins near the end of life, however, but instead is an accumulation of changes and experiences that started at the beginning of the life of an animal. Patterns of gene expression are altered in response to stresses that could happen at any point in an organism’s existence, or even the existence of its parent. Those modifications in genetics have been shown to significantly impact longevity and health, although the mechanism is unclear.
It’s known that mild stress on mitochondria can have a beneficial impact on the lifespan of an organism. The nematode C. elegans exhibits one of the most impressive examples in which early events have profound effects on longevity; mitochondrial perturbation during development nearly doubles the animal’s lifespan. The nature and timing of such stress is critical. If it happens too early or late, or is too acute in intensity, it can be detrimental to lifespan. When mitochondrial dysfunction occurs later in life, it has deleterious effects and directly contributes to pathologies associated with age-onset neurodegenerative diseases. This phenomenon is incredibly conserved and can be observed in yeast and flies, as well as mice.
In a new study reported in Cell
, investigators from the University of California, Berkeley and the École Polytechnique Fédérale de Lausanne in Switzerland looked at several enzymes that play key roles in mitochondrial homeostasis. When mild mitochondrial stress occurs during development, there is an increase in the amount of these enzymes present. They also have an effect on gene expression that continues throughout the life of the organism. The researchers checked the levels of them in mice with different lifespans and found that the longer the lifespan of the animal, the more enzyme present.
“Two of the enzymes we discovered are highly, highly correlated with lifespan; it is the biggest genetic correlation that has ever been found for lifespan in mice, and they’re both naturally occurring variants,” said Andrew Dillin, who is a UC Berkeley professor of molecular and cell biology. “Based on what we see in worms, boosting these enzymes could reprogram your metabolism to create better health, with a possible side effect of altering lifespan.”
This is the first report of epigenetic modifiers that can affect metabolic function and longevity, although there are others that are known to affect either metabolism or lifespan. Through epigenetics, much remains to be discovered about how lifestyle and environment can have a big influence on not only our lives, but also the lives of our descendants.
, Berkeley News