Fight Aging!

The author of this commentary is entirely too enthusiastic about mTOR inhibitors as a tool to slow the aging process, but here he is largely focused on a different question. He argues (a) the sensible point that limits to aging and longevity are entirely determined by medical technology, and (b) the more debatable point that old people do not receive sufficient application of present forms of medical technology, and this is life-limiting. How much of the observed compression of morbidity of recent decades, meaning that people are living more healthy, functional years without an increase in overall life expectancy, is the rest of uneven application of incremental advances in medicine, where the younger old are treated but the older old are not?

My view of the existence of compression of morbidity has long been that some processes of aging must be largely unaffected by everything achieved to date in the field of medicine, while also only contributing greatly to mortality in very late life. So a process that is of little influence up to age 70, say, but which becomes increasingly harmful after that age. Transthyretin amyloidosis might be a candidate for that process, given the findings that it is a major cause of death in supercentenarians. Equally, more recent data is implicating it in heart disease in younger demographics, so perhaps it isn't.

As to the bigger picture: we are complex machines, and the more effort put into maintaining a machine, the longer it will remain in a good state, working and functional. There is nothing magical about aging, it is just damage and dysfunction. That we cannot sufficiently repair that damage or greatly influence the consequent dysfunction today does not mean that there is a limit to life span, set in stone. That limit will be changed tomorrow. Indeed, I would it expect to make a sizable leap upward as a result of the use of senolytic drugs in conjunction with other SENS-style approaches to rejuvenation, as they emerge from the labs and into clinical practice. If compression of morbidity continues in that environment, then it will mean that the research community has not yet targeted the most important forms of damage and dysfunction in the oldest of people.

No limit to maximal lifespan in humans: how to beat a 122-year-old record

Life expectancy is constantly rising and median lifespan is increasing but maximum lifespan is not. Although the number of centenarians (100 years old or older) is doubling every ten years, maximum longevity remains the same. The longest living person died in 1997 at the age of 122 and this record has not been beaten. It was suggested that longevity records cannot be overcome unless a scientific breakthrough in delaying aging would happen. First, such scientific breakthroughs are happening now and drugs that slow down aging are becoming available. Yet, these drugs have not yet been employed in a sufficient number of humans for a sufficiently long period of time to make demographic impact. This breakthrough will eventually break the lifespan record. However, such a breakthrough is not even necessary. A mere application of standard medical care to centenarians, as rigorously as to younger adults, would probably extend lifespan beyond 122, even without the need of a scientific breakthrough.

We will discuss here that an increase of average lifespan without maximal lifespan is happening because advanced medical interventions are available for everyone except the oldest old, exactly those who may live longer than 122, if treated. While a thirty-year old patient with heart disease may become a candidate for heart transplantation, it would be ridiculous even to mention heart transplantation for a supercentenarian. In other words, life-extending care is not available (usually with best intentions; in many cases, patients themselves do not want aggressive medical interventions) exclusively and specifically to those who can beat the 122 lifespan record. Furthermore, since their death certificates state "old age" instead of a specific disease, most centenarians do not receive treatment but even a diagnosis. As we will discuss, this explains why the 122 year record is not broken despite the absence of any biological constraints.

The lifespan of slowly aging centenarians can be extended by providing them adequate medical care. But can an average person beat the 122-year-old record? Currently, medical interventions extend lifespan mostly by extending morbidity span. By now several interventions were shown to increase healthspan and lifespan in animals. Hypothetically, these interventions may transform an average person into a slowly aging centenarian.

Rapamycin and everolimus are available to delay age-related diseases and increase health span in pets and humans. Rapamycin-based therapy may include medications such as metformin, aspirin, angiotensin-2 antagonists, PDE5 inhibitors, DHEA, melatonin and several others as well as fasting or low carb diets. In theory, anti-aging therapy may make an average human resemble centenarians, aging slower and developing diseases later. Due to anti-aging treatment, these centenarians will reach 100 in good health, just as genetic centenarians. These centenarians should seek thorough medical care, according to their lower biological age, not according to their chronological age. This, however, will require the revolution of policies, ethical standards and legal issues to ensure maximum longevity.