Fountain of Youth

Maximum lifespan is defined as the maximum number of time members of a species have been observed to live. According to the Hebrew Bible, Methuselah lived until the age of 969. More contemporaneously, Jeanne Calment, holds the distinction for the longest recorded human lifespan of 122 years. When she was born in 1875, the germ theory of disease had just been discovered and there was no notion of the concept of the gene. At the time of her death in 1997, the human genome was nearly sequenced to completion. In fact, most of medicine was developed during her lifetime. In contrast to lifespan, life expectancy is a statistical measure of the average time an organism is expected to live and it is often quoted as life expectancy at birth. Just like any average it is disproportionately impacted by extreme values (young or old) in the distribution.After thousands of years of slow but steady increases, we had an exponential increase in life expectancy at the turn of the 19th century. This increase was the direct result of the products of scientific inquiry of the Renaissance. We began to  develop more efficient technologies (refrigeration, sewage disposal, clean water, indoor living and working environments) to protect modern populations from the hazards of the outside world such as accidents, infectious diseases, and predation. These advances extended the lives of the young. However, now that we have achieved those gains in infant mortality, the only significant way to increase life expectancy in the future is to generate dramatic reductions in death rates at the oldest ages and simultaneously push the envelop of survival into the outer regions of the lifespan.

In 1825, the British actuary Benjamin Gompertz discovered the law of mortality (known today as Gompertz law). He found that mortality increases in geometrical progression with the age of adult humans. According to the law of mortality, human mortality rates double every 8 years of adult age. Additionally, mortality rates includes not only an aging function (ie age related degenerative diseases) but also a non-aging function (ie accidents, acute infections). The Gompertz-Makeham law of mortality states that that the death rate is the sum of the age independent function and age dependent component. There is an increase in the rate of death as age increases after sexual maturation until the eighth or ninth decade of life. This increase is largely due to the age dependent function. In other words, the biological processes of aging drives the mortality rate after sexual maturation. Therefore, if we are to have any further gains in life expectancy, we will have to alter the process of aging itself. Thus far, there is no evidence that the prospects for surviving past the age of 110 are improving. In fact, if you look at survival curves, mortality has shifted into a fairly narrow range between the ages of 65 and 90. This observed statistical phenomenon is known as the compression of mortality.

Twenty five percent of the world’s burden of disease is attributable to illness in adults aged 60 years and older. Seventy percent of the older-adult disease burden is due to noncommunicable diseases (NCDs) such as heart disease, cancer, chronic respiratory disease, musculoskeletal conditions, and mental disorders such as Alzheimer’s and dementia.¹ However, these chronic diseases are only proxies to the root cause – senescence. Interestingly, if you look in nature, there are numerous organisms that do not show signs of aging nor functional decline. This process – termed negligible senescence – also exists in humans at extremes of age. If you look at mortality rates, they  paradoxically decelerate late in life resulting in distinct mortality plateaus. Is there a physiological basis for this tantalizing tapering or is it just a statistical observation? If the former is true, then hacking into the mechanisms underlying this tapering process at an earlier stage in life, could potentially curb mortality rates, extend the above mentioned compression of mortality, drive increases in lifespan past the current 125 year theoretical limit, and thereby, increase life expectancy.  

¹ Martin J. Prince, Fan Wu, Yanfei Guo, Luis M. Gutierrez Robledo, Martin O’Donnell, Richard Sullivan, and Salim Yusuf, “The Burden of Disease in Older People and Implications for Health Policy and Practice,” The Lancet 6736 (14) (2014): 100– 111.