Muscles, aging and HIV. At first glance, the items on this list seem to have little to do with each other, but it turns out there are deep biological connections between them that could enhance our knowledge of several important conditions — from aging and HIV to diabetes and diseases of the muscles.
Monty Montano, PhD, is at the forefront of exploring these hidden connections. He joined BWH in September as a new faculty member and director of Muscle and Aging Interventions. He is pursuing a multi-pronged approach and bringing together groups across BWH and beyond to gain a better understanding of muscle wasting and its role in normal biology and disease.
What drew you to BWH?
There are two big reasons why I joined BWH. The first is to develop a program of research focused on muscles and aging, and to address the complications that arise in patients with HIV, even those receiving treatment. It has been observed that patients with HIV seem to undergo an accelerated aging process, so part of my work is to explore whether or not people who are on HIV treatment — who ostensibly seem fine — are in fact getting weaker faster. This requires someone who understands the HIV epidemic, but who also has been engaged in research on muscle strength and maintenance, as well as aging. I’m really thrilled to be here.
My research requires a truly multidisciplinary approach, one that draws upon the expertise of several departments within BWH, especially the Infectious Diseases Division and the Division of Endocrinology. I’m excited about what lies ahead and look forward to working with colleagues throughout the hospital.
This isn’t your first stint at a Harvard-affiliated institution, is that right?
Yes, I did my postdoctoral work at the Harvard School of Public Health, with Max Essex, DVM, PhD, Mary Woodard Lasker Professor of Health Sciences. Now, looking out of my BWH office, I can see the building where I worked as a postdoc. That’s pretty neat. I’m coming back home in a way.
What led you to pursue these various lines of research?
When I was a postdoc, I traveled to sub-Saharan Africa to design and build an HIV reference lab in Botswana. The AIDS epidemic there was greater than anywhere on the planet. Anti-retroviral therapy was just being rolled out and many studies were about to get underway.
What really struck me, though, was the severe muscle wasting that accompanied the disease — something these drugs didn’t address. It was very powerful to see people affected by this horrible “side effect” of the disease. I really wanted to understand why muscle wasting was occurring and that led me to begin looking at muscle research and muscle wasting more generally.
I learned that wasting takes many forms. It occurs in cancer as a condition called cachexia. Up to 20 percent of people with cancer die from this wasting, not the actual cancer. It also emerges as healthy individuals grow older through a condition called age-associated sarcopenia. This is the decline in muscle mass and physical function — the effects of the inexorable march of time — that strikes people as they age.
So, I began to do research on muscle biology and muscle stem cells, and how they contribute to muscle maintenance. I also started to work on aging. And finally my research came full circle, so to speak, as I’ve been exploring whether HIV is a disease of accelerated aging by focusing on muscle mass and muscle function in patients chronically infected with the virus. The patients will all be on therapy, and our preliminary evidence suggests that fibrosis (or the development of fibrous connective tissue as a reparative response to injury or damage) may be driving declines in physical function. This is something we hope to learn more about in the MATCH (Muscle and Aging in Treated Chronic HIV infection) study.
What are some of the most interesting projects you are working on now?
I’m really excited about this upcoming NIH-sponsored study we are planning that seeks to enroll 200 people — 100 with HIV and 100 without. Participants will be 50 years and older, with those who are HIV positive receiving regular anti-retroviral treatment. The plan is to closely follow these people over time (initially five years), both through the lens of an infectious disease physician and through the lens of a geriatric endocrinologist. We really want to home in on this question of whether or not there is accelerated aging in HIV and if so, what that really means.
I don’t think we’ll find that every aspect of aging is accelerated. Based on my work on the genetics and molecular pathways of aging, there is likely to be a concerted set of transitions throughout the aging process. In HIV, we think that some of these aging pathways may be out of sync — not accelerated, so much as out of step. It is this asynchrony in pathway expression that likely leads to tissue dysfunction and physical decline.
How can industry play a role in this area?
I think industry has a very important role to play, and I believe strongly in it. This is the second big reason I joined BWH. In addition to my academic role at BWH, I’m also the founder of a company called MyoSyntax. The company is focused on using evidence gleaned from research studies and providing that research as information for individuals to use as they navigate the world of over-the-counter (OTC) vitamins and supplements, and sometimes prescription drugs, for maintaining health, including muscle mass and function, and for preventing decline.
Usually, people choose these types of products based on branding —‘Arnold Schwarzenegger uses this, so I should use it.’ But the thing is, these supplements don’t necessarily work for everyone. For example, even testosterone doesn’t work effectively for everyone, with 20 percent or so of people being non-responders. MyoSyntax aims to use evidence-based information, rather than branding, to guide personalized use of these supplements for non-responders and people who need help in maintaining their muscle mass, their muscle function and their quality of life.
You recently convened a half-day symposium. What was its focus?
The symposium was the first of a series of three events over the next academic year that will focus broadly on translational studies in muscle and aging. In November, we focused on frailty in HIV and aging. In March, we’ll address the topic of clinical trial design and possibly exercise as synergistic intervention for functional decline, and in May, we’ll take up the issue of fatigue, examining everything from the brain to muscle. The symposium series is motivated by strategies to maximize the quality of life — not just living long, but also living well.
A goal of these events is to bring together key thought leaders on muscle maintenance from across academia and industry. An important part of what I want to do here at BWH is to be effective and efficient in our research discovery as well as the implementation of those discoveries. It is a real testament to the innovative spirit at BWH to be able to figure out a platform and a structure that optimizes the synergy between academic and industry initiatives that are put forward by the faculty. Developing this symposium series is one step in that journey.