Aging is a complex, multi-stage process and therefore difficult accurately quantify using a single number, such as biological age.
In a new study reported in Nature Communications, scientists quantify the aging process in humans in a variable they call the dynamic organismal state indicator (DOSI) that is a log-linear mortality estimate computed from complete blood counts (CBC).
The development of this computational cue is aimed at facilitating a systematic investigation of the aging process and the development of reliable biomarkers of human aging. A quantitative understanding of the relationship between the slow dynamics of biological processes, recovery rate from disease or injury (resilience), and the exponential acceleration of morbidity and mortality will allow the rational design, development, and clinical validation of effective antiaging interventions.
The study, an international collaborative effort, is based on a large longitudinal database of CBC collected as part of CDC’s NHANES (National Health And Nutritional Examination Surveys) and UK Biobank, and the findings are reported in the article, “Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts human lifespan limit.”
Recent studies show choosing healthy lifestyles, quitting unhealthy habits, and other experimental interventions can increase human lifespan. However, in the absence of a measure that accurately estimates the change in biological age over time, it is difficult to interpret the efficacy of antiaging interventions.
To quantify the aging process in humans, scientists at a Singapore-based biotech company, Gero, collaborated with biologists and biophysicists at the Roswell Park Comprehensive Cancer Center in Buffalo NY, and three research institutes in Russia.
As expected, resilience or the rate of recovery is quicker in healthy humans but deteriorates with age. While healthy 40-year-old humans take around two weeks to recover, this stretches to six weeks for the average 80-year-old. The researchers quantitatively confirm this finding in two independent biological measures, blood test parameters and physical activity levels recorded by wearable devices on the other hand.
Extrapolating this ability to recover shows that at an age between 120 and 150 average humans not suffering from major chronic diseases will completely lose the ability to recover, thereby estimating the absolute limits of human lifespan.
The predicted loss of resilience even in the healthiest, most successfully aging individuals, might explain why we do not see an increase of the maximum lifespan, while the average lifespan has been steadily increasing with medical advances.
“Aging in humans exhibits universal features common to complex systems operating on the brink of disintegration. This work is a demonstration of how concepts borrowed from physical sciences can be used in biology to probe different aspects of senescence and frailty to produce strong interventions against aging,” says Peter Fedichev, PhD, co-founder and CEO of Gero.
The computational model indicates that no extension in maximum lifespan is possible by preventing or curing diseases without interception of the aging process that causes loss of resilience.
“This work by the Gero team shows that longitudinal studies provide novel possibilities for understanding the aging process and systematic identification of biomarkers of human aging in large biomedical data. The research will help to understand the limits of longevity and future anti-aging interventions. What’s even more important, the study may help to bridge the rising gap between the health- and lifespan, which continues to widen in most developing countries,” says Brian Kennedy, PhD, Distinguished Professor of Biochemistry and Physiology at National University Singapore.
“This work, in my opinion, is a conceptual breakthrough because it determines and separates the roles of fundamental factors in human longevity—the aging, defined as progressive loss of resilience, and age-related diseases, as “executors of death” following the loss of resilience. It explains why even most effective prevention and treatment of age-related diseases could only improve the average but not the maximal lifespan unless true antiaging therapies have been developed,” says Andrei Gudkov, PhD, Sr. vice president and Chair of Department of Cell Stress Biology at Roswell Park Comprehensive Cancer Center, a co-author of this work and a co-founder of Genome Protection, a biotech company that is focused on the development of antiaging therapies.
“The investigation shows that recovery rate is an important signature of aging that can guide the development of drugs to slow the process and extend health span,” says David Sinclair, PhD, Harvard Medical School professor of genetics as an expert unrelated to the study.
The collation of individual physiological data from wearables biosensors such as ones used in this study can help create longitudinal profiles and provide insights on complex processes of aging.