As you walk toward the doors of a gymnasium that you vaguely recognize, your hand clasps tightly around your partner's. The early summer heat isn't entirely to blame for your sweaty palms, and you feel your nerves and excitement begin to rise, your heartbeat pounding along with the crescendo sounds of a drumbeat emanating from the open doors. Just outside, a woman sits at a foldout table handing out name tags. As you approach, she smiles, glances at her list, and hands you the white sticker with your name printed neatly on it. "How are you? I am so glad you made it!" she says. "I'm good," you reply reflexively. "It's great to see you too. This should be a fun evening!" As you utter the words, you hope it'll be true-after all, it's your thirtieth high school reunion.
As you enter the gym that is currently masquerading as a ballroom, your eyes slowly adjust to the dim lighting. In front of you are dozens of people talking, laughing, drinking, and a few quickly catching your eye as they assess the newcomers to the party. You can identify many of them, but others cast only a flicker of recognition across your mind-faces you're sure you have seen before but can't quite place. Just to your right, however, is a woman you would know anywhere. She is dancing exuberantly with a small group as they laugh and attempt not to spill the contents of the drinks they are clutching. It is Maggie, and aside from the hairstyle, she hasn't changed a bit over the past three decades!
As you start walking over to say hello, you feel someone tap your shoulder. When you turn around, there is a man in front of you, grinning-his arms held up in a Hey, it's me gesture. "Wow!" he says "It is so great to see you! I can't believe it has been so long." Suddenly those nerves you felt earlier in the evening are back. You cannot place the face that is smiling back at you. This man who is probably just shy of fifty years old doesn't resemble any of your former teenaged friends. Thankfully you remember that everyone is wearing a name tag-likely for this exact purpose. You quickly steal a glance down at his. "Wow, Doug! I can't believe it's you . . . You look great!" You hope you are better at lying than name recall, and for a second you worry that the reason you couldn't remember Doug's name was because of some sort of age-related memory loss. No, that's crazy, you realize. You're not even fifty. You are healthy as can be, and besides, that won't ever happen to you . . . Or will it?
Suddenly you're struck with the alarming realization that there are surely people in this room that it will happen to, and perhaps in the not too distant future. Of your two hundred classmates there tonight, statistics predict that only half of you will survive the next thirty years. Who will make it to a sixtieth reunion? What will you be like if you make it? Will you have more stories to share of loss or narrowly won battles against disease? Will Maggie be dancing as if nothing has changed except perhaps the absence of some much missed friends?
As you scan the room, you realize that you can make a few educated guesses about who will be in attendance. Even though you're only in middle age, it's clear that some trajectories have already started to diverge, accelerating toward the destiny that awaits all of us. Yet for others, time seems to have mysteriously stalled shortly after graduation. Where do you fit? Will you be one of the lucky ones? And is there anything within your power you can do to ensure you see this gymnasium again through the eyes of your eighty-year-old self?
Biological Versus Chronological Age Most of us know how many years, and perhaps even how many days, have passed since we were born. But is chronological age really just a number? Deep down, do you know how old-or better yet, how young-you really are? We have all thought about it. As humans, we are innately aware of the changes that seem to coincide with every passing year. We know mortality is imminent and that something about aging slowly draws us toward it.
Time appears to have an inevitable impact on our bodies, our minds, and perhaps even our identity. But while aging is universal, the continuous march of time doesn't intrude on all of us equally. The fleeting years are harsher for some, bringing with them disease, impairment, and loss. For others, the passing of time is only evidenced by the smooth creases at the corners of their eyes, or the indelible remnants of past smiles. The explanation? We all age at different rates and in different ways. While our chronological age may increase at a constant and universal rate, signified by the number of candles on our birthday cake, the same cannot be said for our biological age, or what I like to call our True Age. And it is this age that we need to pay better attention to.
Biological age-not chronological age-is what underlies the changes we see in the mirror. The changes we feel as we rise out of bed each morning. The changes that cause most of the diseases and conditions that plague living creatures as they grow old. We have been conditioned to care about our chronological age. To hide it or feel ashamed of it. But the opposite should be true. Our chronological age is a badge of honor. It represents our accomplishments, memories, and the moments spent with loved ones. It captures all the beautiful things that make life worth living. But the best, and perhaps only, way to truly earn more chronological years is by taking up arms against its unfortunate companion-biological age. Luckily, both nature and science have shown us that this is possible to a degree, and that in many ways, you hold the key.
Why Aging Really Matters People often ask me how I became interested in aging. My mother is a professor who studies public policy and works toward improving health outcomes and quality of life for older adults. Her research and outreach help to build safety nets for those whose biological age has rendered them vulnerable to physical, social, and cognitive threats. While this likely influenced my career, I think it was my father and my circumstances growing up that motivated me to dedicate my life to the science of biological aging. As far back as I can remember, I've been fixated on the inevitability of mortality and the realities of growing old. My father was fifty-four when I was born-a retired actor who embraced the role of stay-at-home dad. While he was always active and vibrant, I knew at a young age that he was different from my friends' fathers. When most kids weren't yet contemplating a world without their parents, at seven or eight I was already consumed with the fear that my father might not be around to see me graduate from high school or college, walk me down the aisle at my wedding, or meet his grandchildren. Much to my relief, my father was able to be there for all of these things, including seeing me earn a PhD and be offered my dream job as a professor at Yale University in the School of Medicine. In fact, my father remained in fairly good health for most of his life, up until losing his battle with stomach cancer at the age of eighty-six, two days before I moved from Los Angeles to New Haven to start my position at Yale-a job focused on studying the science of aging.
Most would agree that my father's survival to the age of eighty-six in relatively good health qualifies as a success. But I often find myself lying in bed and contemplating what I wouldn't give to have ten, five, or even one more good year with him. I imagine this is a sentiment shared by most people who lose loved ones to tragic diseases like cancer, heart disease, stroke, diabetes, or Alzheimer's disease. These surprise losses feel beyond our control. When my dad received his cancer diagnosis, I felt helpless. Yes, we can turn to medical professionals in the hope that some treatment may prolong our loved one's time on Earth, but what we all too often fail to recognize is that the process that put the situation in motion has been unfolding for decades. Perhaps since birth.
This is because all of these diseases are caused by biological aging. It is not chronological time itself that renders each of us more susceptible to disease, but rather the biological changes taking place among the molecules and cells in our body that serve as the foundation from which diseases arise. Simply put, biological aging is the single greatest risk factor for disease and death.
Whenever I teach a class on aging, I start by asking my students what they think the biggest risk factor is for lung cancer. Many assume it's smoking. There is no debating that cigarette exposure has an enormous impact on lung cancer risk. According to the Centers for Disease Control and Prevention (CDC), smokers are fifteen to thirty times more likely to develop lung cancer than nonsmokers. The correct answer, however, is actually "aging." The National Cancer Institute estimates that the risk of developing lung cancer in your twenties is less than 1 in 200,000, yet in your seventies the risk becomes eight hundred times greater. Again, this is not something to do with chronological time. Rather, the lung tissue of a seventy-year-old is inherently different from that of a twenty-year-old. The same goes for nearly every organ, tissue, and cell type in your body. As the years pass, we will diverge from the biology of our former selves. Small changes, driven by damage-or just living-will accumulate in all of us. The rate of that accumulation, however, and thus how far we diverge over time varies for each of us, and this has a direct impact on our future health and well-being.
While it remains unclear which kinds of aging-related changes pose the greatest threats, in my lab at Yale, we are developing methods that enable us to track many of these changes, with the hope of eventually discovering how to slow or even reverse them. As of now, we can clearly show that individuals who have accumulated more biological age changes than what would be expected based on their chronological age tend to be at greater risk of death and multiple diverse diseases.
Down the road from my lab at Yale sits a modern glass-and-brick building rising high above most of the surrounding structures. This building houses the Smilow Cancer Hospital and the Yale Cancer Center, where, in addition to treating patients, scientists and medical doctors perform cutting-edge research into the causes and consequences of cancer. Through my involvement with the center, I have had the opportunity to develop exciting research collaborations with many of the other members, including two oncologists, Dr. Erin Hofstatter and Dr. Lajos Pusztai. Through this collaboration, our team's goal has been to understand how age-related changes in breast tissue and/or blood impact the risk of cancer. Tracking age-related markers may facilitate prevention or allow us to identify cancer cases much earlier in the disease process.
One of the most common prevention measures in breast cancer treatment is the mastectomy. First performed in 1889 by Dr. William Halsted, it was shown that removal of the tumor and surrounding breast tissue led to a reduction in local recurrence rates. Later, this proved to be the case only for women whose cancer had not yet spread to nearby lymph nodes. Unlike the somewhat barbaric mastectomies of Dr. Halsted's time, today's procedures remove one or both breasts while attempting to spare the skin and underlying muscle.
While this procedure is done to save patients, the tumors and surrounding tissue that is removed can also provide scientific hints into the causes and potential treatments of breast cancer. Through our collaborative efforts, our team of scientists examined the signs of aging in the surrounding breast tissue from women who underwent mastectomies to treat breast cancer, as well as women who underwent elective procedures to remove breast tissue, either as a preventive measure or to achieve reduction. In both cases, we extracted DNA from what is considered the "normal breast tissue," meaning that even in women with cancer, we are not looking at the DNA from the tumor itself. We then used these samples to estimate how biologically aged the breast tissue was-I will expand on how this is done in chapter 2.
What we discovered was that when comparing the biological ages between women with equivalent chronological ages, breast tissue from women with cancer appeared biologically older than the tissue from women without cancer. While one possibility is that having cancer may accelerate the aging process in nearby healthy tissue, we think the more likely scenario is that women who have accelerated aging in their breast tissue may be more prone to developing breast cancer. The same may be true for other cancers-aging-related changes in the tissue can promote tumorigenesis.
We have also shown that this finding is not just specific to cancer. For instance, we looked at aging in brains using the exact same method applied to predict biological age in the breast samples. What we have found is that individuals who have biologically older brains at autopsy (regardless of chronological age) are more likely to be riddled with the hallmarks of Alzheimer's disease. Similarly, when estimating aging in lungs, those with a chronic lung disease called "idiopathic pulmonary fibrosis" were biologically older, and when estimating aging in livers, fatty liver disease was associated with older biological age. Across the board, time and again, biological aging in different organs appears to drive the development of disease. What's more, beyond promoting the progression of diseases that take decades to develop, biological aging may also make us more vulnerable to spontaneous threats-as in the case of viruses.
Copyright © 2022 by Morgan Levine, PhD. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
