Frailty in Extended Lifespans

Whenever the topic of increasing human lifespan is discussed, the concern is sometimes raised that a longer life would mean a life spent frail and decrepit. This is sometimes known as the Tithonus error and shows a fundamental misunderstanding of the aims of rejuvenation biotechnology.

The concern is based on the ancient Greek myth of Tithonus, which might be thought of as a cautionary tale that warns seekers of an eternal life of its alleged inherent dangers.

The myth of Tithonus in brief

Tithonus, the story goes, was a mere mortal who was in love with Eos, the beautiful titan of the dawn. His feelings were requited, but, unfortunately, their idyll was not destined to last. Being a titan, Eos was also a deity and thus immortal, unlike Tithonus, who one day would die of old age if not of some other cause. Eos thus turned to Zeus and asked him to make Tithonus immortal as well. Zeus granted Eos’ wish, but even this did not solve the two lovers’ problem; the father of the gods had granted Tithonus immortality, not eternal youth.

Tithonus never died, but he kept aging like any other mortal; eventually, he was so decrepit, disease-ridden, and demented that his life had become unbearable. According to some tellings of the story, the result of this everlasting aging process was that Tithonus became a cricket, begging for death to come and put an end to the prison that his immortality had become; other versions say it was Eos herself who, moved to pity for her lover’s sad fate, decided to change him into a cricket.

We can guess the lesson to be drawn from this tale: Immortality may sound appealing, but there are drawbacks that make it more of a curse than a blessing.

This can’t actually happen

This type of concern is typically raised by people who don’t have a clear picture of rejuvenation biotechnologies and fear that an extended period of frailty and decrepitude may be the result. Thankfully, quite the opposite is true, and Tithonus’ grim fate is physically impossible.

In the fanciful realm of gods and myths, anything goes and the impossible becomes mundane, but in the real world, neither Zeus nor anyone else could make you live forever without eliminating or obviating the physical aspects of aging. This is because death is nothing but the result of a critical failure of your inner workings; if you died, it means something crucial in your body stopped functioning properly and thus triggered a cascade of failure whose ultimate consequence was your death.

In particular, in the case of death by old age, the critical failure is caused by one or several pathologies driven by the hallmarks of aging. The processes of aging are slow but insidious, and most of them speed up considerably after middle age. Frailty, weakness, and all the notorious diseases of old age are the primary consequences, and they are due to the fact that accumulated damage prevents your body from functioning at its best; when the damage is extensive enough, your body cannot function at all anymore.

A longer life would not mean never-ending, increasing decrepitude

Living forever while aging forever would thus be equivalent to a human-made machine still functioning despite all of its mechanisms being eventually completely broken, which is a contradiction in terms. Another way of seeing it is imagining a house that remains a house even though you keep removing its bricks one by one.

To better illustrate this point, consider stem cell exhaustion, one of the hallmarks of aging. In a nutshell, this means that your bodily tissues lose their building blocks over time; normally, functioning cells are replaced by dividing stem cells, but during old age, this ability is impaired and, consequently, your tissues waste away.

As our stem cells become depleted, we become more fragile and sick, but as long as our tissues have enough cells to perform their job, we will stay alive, although our quality of living will be impaired. Once a tissue has lost enough cells, it can no longer perform its function, and it’s easy to see how this may lead to death; for example, if you lose too many pacemaker cells, your brain will be unable to tell your heart to beat.

More generally, in the legend, Tithonus kept on living for centuries despite that he continued to age, his internal organs kept wasting away, eventually disappearing altogether, and yet somehow they still functioned! Talk about having your cake and eating it too.

So, if you are concerned that a longer life would mean never-ending, increasing decrepitude, you can heave a sigh of relief. It won’t happen because it can’t happen.

What is rejuvenation biotechnology all about, then?

A very small-scale version of Tithonus’ myth does actually take place as a consequence of geriatric medicine. Geriatric medicine focuses on treating the symptoms of age-related diseases rather than their causes, with the result of modestly improving patient health and lifespan; in other words, although undertaken with the best intentions, geriatrics does prolong the time that patients spend in decrepitude.

They live a little longer because mitigating the symptoms slightly postpones the inevitable, but as age-related damage keeps accumulating, eventually the point of no return is reached. It’s a bit like trying to empty a river using a coffee mug.

Rejuvenation biotechnology proposes a different approach, intervening directly in the damage-causing age-related pathologies and repairing or obviating them. For example, in the case of stem cell exhaustion, stem cells could be generated outside the body and used to periodically replenish tissues, thus preventing organ and muscle wasting.

Interventions for different types of age-related damage, such as senolytics for senescent cell clearance, enzyme replacement therapy to dispose of intracellular waste, and AGE-breaking molecules to eliminate extracellular cross-links, are currently being developed, and some are even undergoing human clinical trials.

Does living longer equal a better quality of life?

In the context of rejuvenation biotechnology, the answer would clearly be yes. The aim of rejuvenation biotechnology is neither extending frailty nor achieving a modest amelioration of an elderly patient’s health; rather, the goal is to comprehensively address age-related damage to allow people to maintain youthful levels of health for as long as they live, however long that may be. This would require rejuvenating cells, tissues, and organs so that the body functions as it did in youth. So the nightmare scenario of being trapped in a decrepit body while staying alive would not happen as the body would look and function as it did in youth.

Sounds like a much better deal than that Eos struck with Zeus for Tithonus, doesn’t it?