R&R#6: Our Foundational Reasons Why

Why did you become interested in health and aging? This is my story.

I have been thinking I would wait to write this article, but a recent event has made me start thinking about it again a lot. Why is research on aging diseases, specifically aging damage so important from an individual perspective?

The event that recently brought this all to the forefront of my consciousness again was a sudden loss of my beloved grandmother in-law, Kamala Patti (Patti meaning grandmother in Tamil). She was a very kind and loving woman who radiated a strong sense of positivity which I felt deeply despite having limited ability to speak with her, as she didn’t speak English. She had the mix of chronic aging diseases particularly associated with diabetes/metabolic syndrome that many of us are all too familiar with, but she was always smiling nonetheless and genuinely loved life. Tragically, one day she had a heart failure event, actually when I was in India visiting her and my in-laws for Kamala’s 80^th birthday celebration (completed a week before).

There was a sense of shock as we saw the events unfold in real time over the course of several video calls despite her being seemingly totally okay just earlier. I cried for the sudden loss of another deeply good person, but I will also say that my understanding of the aging process (and my previous specialized experience covering heart failure as a topic while working as a consultant) led me to understand quite well that such things often happen suddenly to those already in poor health. I reflected on what a difference it would make to the human experience to live without that decline, and how people like her deserve to have smart, ambitious individuals fighting for them with the zeal that is warranted.

I first got interested in the field due to my grandmother and grandfather’s deteriorating conditions in my teens and into my early 20s. Their ailments were both earlier-onset aging issues, in essence two sides of one coin. My grandma, Donna, had the very classic trajectory of metabolic syndrome-accelerated aging disease I noted for Kamala Patti. In her case it was exacerbated by a poor lifestyle and some mental health issues. She was obese since before I was born (when she was in her late 40s) and had a type-2 diabetes diagnosis fairly early on. Though some of the details are fuzzy to me, she ended up developing chronic heart failure, a number of diabetic complications, liver fibrosis (despite not having drank alcohol) and towards the end in her late 60’s vascular dementia as well (this list is non-exhaustive and just what I know). Starting around 65 she would regularly be taken to the ER. I believe at least some of the situations were heart failure decompensation events, and she was largely taken care of by my angel of an aunt throughout. Her death was from an acute heart failure episode and also listed as “complications of diabetes”, and as diabetes is to a large extent accelerated aging damage with an accentuated glycation component this was largely accurate. Her body had accumulated so much damage, and strayed so far from being able to manage homeostasis, that it was not as if she went from 100% to 0% in a day- she went from 100% to 40% over three decades, and when one day she briefly slipped to 30% she subsequently crossed over a cliff.

Many readers will likely relate from direct experience with a relative of their own. The result, as usual, is a mix of sorrow and inevitability after death which stems from the fact that we know consciously that the slide can and will end in only one way. But, I saw that my grandma deeply and openly wanted to live, right until the end. As she struggled in every way possible, this just became more true. I wanted to do something about it, and I was a biology major who had already become very passionate about aging. At her funeral, I vowed to remember that this was my grandma who I loved so much who would have been there walking and healthy sans the ravages of aging, not “would have been there in a wheelchair with oxygen sans the last heart failure event”. I emotionally gave a speech vowing to dedicate my life to do better for her where most would not.

My grandpa, Michael, was different. He was a very calm man, contented in a way people with much more than him rarely manage. This was also true after he was diagnosed with Parkinson’s at the age of 37, and continued to be true largely until my grandma passed away 2 years before he did at 69. Yes, he spent 32 years struggling to walk, then to talk, then to think as a result of a few hundred thousand neurons lost in one part of his brain. These neurons, dopamine neurons from the substantia nigra, which may well have had a genetic susceptibility in his case but also which are generally very susceptible to traditional forms of aging damage such as mitochondrial and lysosomal issues. I admired him as he lived his life happily in spite of it all, but I also knew he’d be much happier to be thriving, and we would all be much happier to see him doing so. I again gave a short and emotional speech vowing to deal with neurodegeneration at his funeral. Maybe it was a bit narcissistic to only focus so much on my own work ambitions in my speech, but I didn’t care because I meant every word and have thus far followed through as best as I can. He remains the only human whom I can’t think about without tearing up.

I know for a fact that many of, maybe the majority of people who have gotten into the aging field have done so for similar reasons. I don’t blame people who personally spend a lot of money to look and feel extra young in their 40s and 50s, in fact if I was rich it would likely be among the self-focused things I would take advantage of. But I am just not motivated at a core values and self-actualization level by such stories and people. I think that part of the idea behind this approach is to show that there are people managing to thrive in youthful glory, but if I were to make the equivalent of a Rinvoq commercial for aging it would look somewhat more like these:

·        Going on a 5 mile run with my grandpa (he absolutely hated running, but whatever it’s my dream)

·        My grandma smiling at a family gathering, no one worrying about her and everyone enjoying her company, and begrudgingly making her epic meatballs with impossible beef for me (very begrudgingly, but she would do anything for me)

·        My grandmother-in law watering her plants and then sitting cross-legged on her swing-chair as she listened to her music

·        An 80 year old woman who always wanted to have a career studying for her MD, coming in with equal cognitive function and ambition and superior life knowledge to a 25 year old

·        A 65 year old man from a poor background who had spent years focused on supporting his kids starting the new business he had dreamed of

·        A 36 year old female assistant professor who wants kids just waiting as she works on setting up her lab and her initial publications, and not worrying about declining fertility (and no one else prying either)

·        A 125 year old walking the Appalachian Trail with his wife to celebrate a century of happy marriage

Lastly, this is all also why I am confident that a real revolution against the chronic diseases of aging has already begun. GLP-1 agonists are blowing up in a big way, and have recently been shown to have direct benefit for reducing adverse cardiac events. Thus, arguably the first class of drugs which will truly treat metabolic syndrome has already hit the market and will be among the most widely prescribed treatments in history (though SGLT inhibitors also have strong results and arguably may have taken that crown). The first clinical trial success at dopamine neuron replacement has already arrived (albeit mainly a Phase 1 safety study). More radical options which will reverse or replace ailing hearts and lungs are in development, some in advanced stages.

So much of this is driven by people with similar stories, most of which we have not heard. If you are also working towards a future without chronic disease, whether a high school student or a tenured professor, research associate or biotech executive, please leave a paragraph or two in the comments. I have heard a lot of moral and ethical arguments about why treating aging diseases is essential, and I’d love to hear more of the personal side that goes with them as well.