Resilience integrates concepts in aging research

Promislow, Daniel E. L.; Anderson, Rozalyn M.; Scheffer, Marten; Crespi, Bernard J.; DeGregori, James; Harris, Kelley; Natterson-Horowitz, Barbara; Levine, Morgan E.; Riolo, Michael L.; Spencer, Steven J.; Valenzano, Dario Riccardo; Hochberg, Michael

doi:10.1016/j.isci.2022.104199

Cited by 19 publications

(9 citation statements)

References 77 publications

(98 reference statements)

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“…Frailty is a systemic condition that leads to functional decline with physical and cognitive impairment. 1–3 Frailty is often diagnosed in older adults with hypertension and diabetes, and both these conditions are associated with endothelial dysfunction and oxidative stress. 4–6…”

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confidence: 99%

SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients

et al. 2022

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Background: Frailty is a multidimensional condition often diagnosed in older adults with hypertension and diabetes, and both these conditions are associated with endothelial dysfunction and oxidative stress. We investigated the functional role of the SGLT2 (sodium glucose cotransporter 2) inhibitor empagliflozin in frail diabetic and hypertensive older adults. Methods: We studied the effects of empagliflozin in consecutive hypertensive and diabetic older patients with frailty presenting at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, from March 2021 to January 2022. Moreover, we performed in vitro experiments in human endothelial cells to measure cell viability, permeability, mitochondrial Ca 2+ , and oxidative stress. Results: We evaluated 407 patients; 325 frail elders with diabetes successfully completed the study. We propensity-score matched 75 patients treated with empagliflozin and 75 with no empagliflozin. We observed a correlation between glycemia and Montreal Cognitive Assessment (MoCA) score and between glycemia and 5-meter gait speed (5mGS). At 3-month follow-up, we detected a significant improvement in the MoCA score and in the 5mGS in patients receiving empagliflozin compared with non-treated subjects. Mechanistically, we demonstrate that empagliflozin significantly reduces mitochondrial Ca 2+ overload and reactive oxygen species production triggered by high glucose in human endothelial cells, attenuates cellular permeability, and improves cell viability in response to oxidative stress. Conclusions: Taken together, our data indicate that empagliflozin reduces frailty in diabetic and hypertensive patients, most likely by decreasing the mitochondrial generation of reactive oxygen species in endothelial cells.

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confidence: 99%

SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients

et al. 2022

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“…Examples of non-stationary press perturbations are climate change, which includes systematic changes in temperature and climate variability over time, 52 repeat expansion disease leading to worsening cellular disfunction, 53 and aging. 54 Stressors are non-stationary because the existence and intensity of stressors waxes and wanes over time. 55 For aging, we refer specifically to changes in resilience capacity such as cellular senescence, increased oxidative damage, accumulation of somatic mutations, ineffective clearance of cellular debris, and low-level chronic inflammation of the brain, and so forth.…”

Section: Observation 4: We Need a Richer Lexicon To Describe Perturba...mentioning

confidence: 99%

Is resilience a unifying concept for the biological sciences?

Reed,

Wolfe,

Romero

2024

iScience

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“…The forest is vulnerable to climate change at tipping points where even a small change in climate (say reduced rainfall) may result in a catastrophic transition to savannah. Age-related brain and behavioral fluctuations may also occupy alternative stable states separated by tipping points (20).…”

Section: Introductionmentioning

confidence: 99%

Age-related behavioral resilience in smartphone touchscreen interaction dynamics

Ceolini,

Ridderinkhof,

Ghosh

2024

Preprint

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We experience a life that is full of ups and downs. The ability to bounce back after adverse life events such as the loss of a loved one or serious illness declines with age, and such isolated events can even trigger accelerated aging. How humans respond to common day-to-day perturbations is less clear. Here, we infer the aging status from smartphone behavior by using a decision tree regression model trained to accurately estimate the chronological age based on the dynamics of touchscreen interactions. Individuals (N = 280, 21 to 83 years of age) expressed smartphone behavior that appeared younger on certain days and older on other days through the observation period that lasted up to ~4 years. We captured the essence of these fluctuations by leveraging the mathematical concept of critical transitions and tipping points in complex systems. In most individuals, we find one or more alternative stable aging states separated by tipping points. The older the individual, the lower the resilience to forces that push the behavior across the tipping point into an older state. Traditional accounts of aging based on sparse longitudinal data spanning decades suggest a gradual behavioral decline with age. Taken together with our current results, we propose that the gradual age-related changes are interleaved with more complex dynamics at shorter timescales where the same individual may navigate distinct behavioral aging states from one day to the next. Real-world behavioral data modeled as a complex system can transform how we view and study aging.

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Resilience integrates concepts in aging research

Cited by 19 publications

References 77 publications

SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients

SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients

Is resilience a unifying concept for the biological sciences?

Age-related behavioral resilience in smartphone touchscreen interaction dynamics

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