Biological evidence of the life expectancy limit in human aging.

Life expectancy (LE) at birth has increased in many countries throughout the twentieth and twenty-first centuries. Future LE values are estimated by extrapolating existing data. However, it remains difficult to determine the LE limit using mathematical models such as the Kannisto model and the Gompertz function due to significant random fluctuations in centenarian mortality rates. There are 12 biological hallmarks of ageing, including epigenetic changes and senescent cells. These microscopic dysfunctions and cellular energy are deeply intertwined, based on the inevitable cellular energy deficiency experienced by the elderly. We recently derived an age-dependence of standard cellular energy for people of healthy body shape. The logistic function taking into account standard cellular energy and also a lifespan Tc strictly reproduced the robust age-specific mortality data for ages under 100 years in many countries, by adjusting two parameters Tc and C. We applied the logistic function to the recent Japanese data with the world's longest LE of 87.5 years and the highest natural death rates in centenarians. Consequently, the logistic function explicitly detected the maximum Tc value of 105, even though the C value continuously increased. By setting Tc to 105 and only increasing the C value, we obtained an achievable upper limit of LE = 98. Then, the survival rate trajectory became rectangular due to the biological effect of cellular energy depletion. The LE values of many countries are expected to reach the Japanese LE of 87.5. Standard cellular energy and Tc in the logistic function were essential to detect the LE limit in the Japanese data.