Genomics of aging
On December 12th Vadim Gladyshev from the Harvard Medical School, Boston, USA, gave a conference in a packed room at the PRBB invited by Roderic Guigó from the CRG. Gladyshev investigates the molecular basis for natural changes in longevity and the biological mechanisms involved in aging.
The first part of the conference focused on the mechanisms of aging. Gladyshev’s main question was: why and how do things go wrong with age?
At the beginning he introduced several aging theories that have contributed most significantly to the aging debate in the research community. Some of them were built in the 50s based on 19th century insights, whereas others are very recent. According to him, these theories are very different, each of them touching on a particular aspect of the aging process and, within that context, each has its merit, but all are incomplete.
He continued with his own view about aging. He suggested that imperfectness of biological processes leads to inevitable damage accumulation – called deleteriome – causing aging. His research group is now characterizing properties of cumulative damage and its impact on the aging process. They also study cancer as a disease of aging.
While the mechanisms of aging and the process of lifespan control may seem highly related topics, he maintained that they are different areas. To explain the difference, he used a metaphor of a river, where a lifespan would be equivalent to the time needed for the water to flow from the mountain to the ocean. According to him, the route of the river can be changed to make the journey longer, just like lifespan of humans can be extended. However, the fact that the river flows because of gravity can’t be changed, just like we cannot change the fact that the aging process occurs because of imperfectness. So the cause of aging is different from the determinants of longevity.
The second part of the conference was about mechanisms of lifespan control, trying to answer the questions: why do cells and organisms live as long as they do? and how does Nature adjust lifespan?
Gladyshev’s research team uses multiple approaches to address this question. One methodology involves studying the genes of exceptionally long-lived mammals, such as the naked mole rat, the Brandt’s bat and the bowhead whale. The Brandt’s bat (Myotis brandtii) is found throughout most of Europe and parts of Asia, and it often lives more than 40 years.
The naked mole rat (Heterocephalus glaber) is a burrowing animal commonly found in East Africa, well-adapted to their underground existence. They are characterized by small eyes, short and thin legs, hairless body (hence the common name) and wrinkled pink or yellowish skin. Their large front teeth are used to dig. This animal can live up to 31 years, the record for the longest living rodent.
Gladyshev’s group recently sequenced and analyzed the genomes of these animals, and they discovered some of the adaptations that contribute to their long lifespans. They also identified general gene expression and metabolic changes that associate with longer life.
In addition to the evolutionary study of long-lived animals, Gladyshev’s lab focuses on cell types that have different lifespan and in long-lived mouse models. They also do analysis across species and cell culture-based profiling in order to find unique and common mechanisms of longevity. Longevity signatures (based on gene expression) identify candidate interventions for lifespan extension. Ultimately, the researchers would like to find treatments or some other approaches which would help extend life span and diminish the consequences of age-related diseases.
At the end of the talk the public showed great interest on Gladyshev’s research, posing many questions about aging in yeast, epigenetic drift in aging and the relation between lifespan and maturity. In a fruitful and interesting conversation, some in the audience also suggested research approaches such as studying aging in single cells or focusing on the physics of aging. We’ll have to wait for Gladyshev’s next talk to see if some of these suggestions gave their fruits!
A report by Mari Carmen Cebrián