·       A new method predicts how biological age affects resilience the rate of recovery from setbacks in health.
·       This model was used to develop a biological sensor phone app to monitor people’s state of health and resilience to measure possible anti-aging effects of therapeutics.

Our chronological age, or how many birthdays we’ve had, doesn’t predict our longevity or attributes like frailty and resilience — how well we can bounce back from a perturbation or stress to our physical and mental health. Although methods that measure the actual age of tissues, organs, and blood called biological clocks are proving to be more telling of how long we will live than just how old we are, most biological aging tests measure individual biological markers that fluctuate, which can lead to inaccurate predictions of aging attributes and trajectory. 

Using a new method that combines measurements of several biological aging markers, Fedichev and colleagues published a study in Nature Communications mapping biological aging trajectories. Interestingly, this model shows that our ability to recover from stress is lost somewhere around 120 to 150 years, representing a limit to human lifespan. Using this framework in conjunction with step counters that are built-in in almost all modern mobile devices, they created a phone app that predicts biological age.

“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 anti-aging therapies have been developed,” said Andrei Gudkov, Ph.D., a co-author of the study in a press release.

DOSI: A New Tool To For Modeling Human Aging

To characterize the trajectory of human biological aging, Fedichev and colleagues developed a method called the Dynamic Organism State Index (DOSI). DOSI combines several measurements like complete blood counts (CBC), which are most frequently included in standard blood tests, from a large dataset of individuals ages 1 to 85 over some time. The Gero researchers found that on average, as the DOSI score increases, so does the risk of disease and death. Also, individuals who were categorized as the frailest had an increase in DOSI scores across their lifespan.

Qualitatively, Fedichev and colleagues differentiated three distinct segments of the aging trajectory, corresponding to (I) early adulthood (16–35 y.o.); (II) middle ages (35–65 y.o.); and (III) older ages (older than 65 y.o.). DOSI values slowly increase during a growth phase until age 30, followed by a slightly steeper elevation in DOSI values starting after age 40. Then, after about age 65, people show exponentially increasing DOSI values with passing years.

(Pyrkov et al., 2021 | Nature Communications) DOSI categorizes biological aging. The plot on the left is a graphical representation of aging for 5 to 85-year-old NHANES participants. There are 3 distinct segments in this plot, corresponding to (I) age < 35; (II) age 35–65; (III) age > 65. The plot on the right (B) shows that multiple morbidity manifests itself as elevated DOSI levels, as seen from the difference between the solid and dashed lines, which represent the DOSI means in the cohorts of healthy (“non-frail”) and “most frail” participants, respectively.

Moving in the opposite direction, an individual’s resilience decreases with an increasing DOSI score. Using this method, they found that people in their forties took about two weeks to recover from stress whereas people in their nineties took over eight weeks.

The Human Lifespan is Limited to 150 Years

The DOSI values fluctuate with age. These fluctuations become greater and more frequent with age. Around age 120 to 150, the fluctuations to a point where returning to normal and stable DOSI values become unobtainable, which Fedichev and colleagues propose represents an inherent limit to our lifespans.

(Pyrkov et al., 2021 | Nature Communications) Physiological state fluctuations and loss of resilience predict a limit to human longevity. The plot on the left shows how the inverse variance of DOSI decreased linearly in all investigated datasets and its extrapolated value vanished (hence, the variance diverged) at an age in the range of 120–150 years old. The plot on the right shows how deviations from normal DOSI values measuring physiological balance increase substantially with age and reach a critical point around age 120 to 150 years, representing the limit to human lifespan. The vertical axis represents potential physiological energy, and as years progress, deviations from stable DOSI values (A) veer toward unstable values (C) with trajectories of the minimum balanced DOSI values (D) declining. During this age-related progression toward the critical value between 120 to 150 years when returning to stable DOSI values is no longer feasible, the energy barrier maintaining the balance (B) loses its significance.

Wearable Technology Provides Extended DOSI Monitoring

Gero developed mobile and wearable biological sensors called GeroSense to gather DOSI data that can be used to calculate a person’s resilience. People can use the GeroSense monitoring technology for biological age calculation based on streams of mobile data from wearable sensors by downloading an iPhone app. By using the app, individuals can monitor any possible effects of anti-aging and pro-longevity therapeutics as well as healthy lifestyle choices on biological age.

“Calculation of resilience based on physical activity data streams has been implemented in GeroSense iPhone app and made available for the research community via web-based API.” – commented the first author of the study, Tim Pyrkov, head of the mHealth project at Gero.

“GeroSense predicts biological age as well as how stable it is and how quickly it will likely change so that we can timely detect anomalies due to changes in lifestyle or health status,” said Peter Fedichev, Co-Founder and CEO, Gero. “This became only possible thanks to non-invasive wearable technology, yet with accuracy similar to that of invasive tests as validated in our recent scientific paper.”