Changing Aging — 2

Over time, the gap between LE and HALE is getting larger, with chronic illnesses on the rise in the United States. That’s why the notion that slowing down aging for one year, a small increase in LE, would be worth $38 trillion, and by ten years $367 trillion in the United States is not far-fetched. If health span is not increased and the gap closed, we’d be adding to the economic burden of long lives with chronic diseases, not reducing it. The only way we might accomplish closing the gap is to slow the aging process, ideally at the whole-body level. If we reduce heart disease but increase the prevalence of Alzheimer’s disease, we’re into competing interests and a Whac-A-Mole model of expanding health span. A longer lifespan gives more chance for all the diseases of biological aging to manifest. People just don’t fall off a cliff healthy. Slowing the whole-body aging process is the only way to bridge the gap.

There’s a fierce debate about human lifespan’s upper limit. Some researchers invoke the Gompertz-Makeham law, which states that the risk of death increases exponentially with age; others invoke the Hayflick limit theory, which posits that human cells cannot divide much beyond fifty times. The age at death of the world’s oldest person—Jeanne Calment at age 122—hasn’t budged since 1997. Beyond biology, there’s the physics of wear and tear, cumulative aging from recurrent stress to our cells, tissues, and body, the obligatory decay that can be loosely attributed to the second law of thermodynamics. In this regard, whether there is an absolute limit is moot, since having more Methuselahs isn’t going to promote healthy Methuselahs. Ideally, we’d want to extend both with no gap, achieving full alignment of HALE and LE. That’s not so simple and will ultimately depend on exploiting the science of aging.

THE BIOLOGY OF THE AGING PROCESS

The process of aging is generally considered to be the accumulation of damage to our cells and molecules over time. Biological hallmarks of the process indicate they occur with aging, their increased prominence accelerates aging, and getting rid of the hallmarks slows aging. The most cited paper on the hallmarks of aging was published in 2013 and updated in 2023. Over the course of that decade, there’s been remarkable progress in the field only touched on by the expansion of hallmarks from nine to twelve (fig. 12.1), with the recent additions of chronic inflammation, the gut microbiome, and waste removal. This breakdown of twelve different processes is a bit arbitrary and reductionist because there is considerable overlap between them. They’re all integrative, even though that’s only one of the three categories (fig. 12.1). However, each hallmark provides “the opportunity to decelerate, halt, or reverse aging by therapeutic interventions.” Indeed, each process is being pursued by multiple companies and interventions. Let’s go clockwise around the hallmark wheel, starting at genomics.