By Evin Adolph
Infoaging Correspondent

Dr. Ana Maria Cuervo

Taking out the trash is usually not something to get excited about. But for Ana Maria Cuervo, MD, PhD, taking out the trash, the cellular trash that is, couldn’t be more of a thrill. As Dr. Cuervo launches into her explanation of the many intriguing and innovative research projects taking place in her lab, it becomes apparent just why her job is so exciting.

Dr. Cuervo’s interest in aging research and her specific field of focus stems from her experiences in medical school. “When I was in medical school, I became very interested in geriatrics, and in particular why some people age so well while others seem to go into such fast decay,” said Dr. Cuervo. “I was very lucky to be accepted into the groups of Dr. Erwin Knecht and Dr. Fred Dice as a post-doc, both of whom introduced me to the field of protein turnover and in particular to lysosomes and the dramatic consequences the loss of function this organelle has on cells and organisms.” Dr. Cuervo has brought her enthusiasm to the lab at Albert Einstein College of Medicine of Yeshiva University, and her work, along with that of her colleagues, has produced astounding insight and potential interventions for diseases associated with aging such as Alzheimer’s disease, Parkinson’s disease, and even cancer and diabetes.

Aging is characterized primarily by the decline of function in various cellular and molecular systems in the body. These changes are influenced by three factors: genetics, metabolism, and the environment. The focus in Dr. Cuervo’s lab is the metabolic changes and resulting damage from these changes that are experienced with age, specifically damage to proteins. Every person experiences this damage to some degree, regardless of their age, but when it comes to repairing or removing the damage, the difference between young and old is clear. In younger people, the damaged or misfolded proteins can be repaired by what are known as chaperone proteins. Yet, like an old car, proteins that have undergone too much repair are not worth maintaining and so they are transported by the chaperone to the lysosome as “trash” where they bind to a receptor and undergo autophagy (literally, self-eating) inside the organelle. Dr. Cuervo’s research focuses on this pathway and how a major decline in its functionality is seen in older organisms.

In older people (and rodents), the deterioration of this pathway prevents the damaged proteins from being digested by the powerful enzymes in the lysosome, thus causing a buildup of aggregate proteins — trash — in the cell. These aggregates are the cause of neuron death as well as the infamous neurodegenerative diseases. After some initial investigation of the pathway, Dr. Cuervo’s attention turned to the receptor on the lysosomal membrane, LAMP-2A. Her research, along with the various off-shoots being examined by her colleagues, focuses on the many different aspects of this receptor and the reason for its decline with age.

Dr. Cuervo’s work with LAMP-2A led her to believe that by supplementing this receptor in older animals experiencing a decline in the function of their own “recycling” pathway, she could remove the cellular trash and thus extend the lifespan of the animal. Her instincts led to the discovery that the addition of LAMP-2A into middle-aged mice reduced cellular protein damage and restored functionality in a 22-month-old mouse (about 80 years for humans) to that of a three-month old (or a 20-year-old human). This incredible information is a momentous step in the direction of curing neurodegenerative diseases, as well as alleviating the discomfort that often accompanies aging. Dr. Cuervo hopes that her findings could result in the production of a drug that would prevent the decline of LAMP-2A with age and thus prevent (or at least delay) many of these devastating diseases of aging from occurring all together.  This drug could be administered to older adults as a sort of annual “cleaning house.”  

It would seem that taking out the trash isn’t such a bad job after all.

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