Early life stress and frailty in old age: the Helsinki birth cohort study

Haapanen, Markus J; Perälä, Mia-Maria; Salonen, Minna K.; Kajantie, Eero; Simonen, Mika; Pohjolainen, Pertti; Pesonen, Anu‐Katriina; Räikkönen, Katri; Eriksson, Johan G.; Bonsdorff, Mikaela von

doi:10.1186/s12877-018-0873-5

Cited by 32 publications

(20 citation statements)

References 36 publications

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“…Our results show that MatSep can alter the levels of specific proteostasis markers in adulthood and in advanced age, in a sex-and brain regionspecific manner. These findings are consistent with the notion of ELS negatively influencing later brain health, as has been previously demonstrated in both animal and human studies (Haapanen et al, 2018;Ruiz et al, 2018). Interestingly, most of the MatSep-induced changes in proteostasis marker expression that we observed in adult animals were not seen in aged animals.…”

Section: Discussionsupporting

confidence: 93%

Neonatal Maternal Separation Modifies Proteostasis Marker Expression in the Adult Hippocampus

Sierra-Fonseca

Hamdan

Cohen

et al. 2021

Front. Mol. Neurosci.

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Exposure to early-life stress (ELS) can persistently modify neuronal circuits and functions, and contribute to the expression of misfolded and aggregated proteins that are hallmarks of several neurodegenerative diseases. The healthy brain is able to clear dysfunctional proteins through the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP). Accumulating evidence indicates that impairment of these pathways contributes to enhanced protein aggregation and neurodegeneration. While stress is a known precipitant of neurological decline, few specific mechanistic links underlying this relationship have been identified. We hypothesized that neonatal maternal separation (MatSep), a well-established model of ELS, has the ability to alter the levels of UPS and ALP components in the brain, and thus has the potential to disrupt proteostasis. The expression of proteostasis-associated protein markers was evaluated by immunoblotting in the hippocampus and cortex of adult Wistar rats that were previously subjected to MatSep. We observed multiple sex- and MatSep-specific changes in the expression of proteins in the ALP, mitophagy, and UPS pathways, particularly in the hippocampus of adult animals. In contrast, MatSep had limited influence on proteostasis marker expression in the cortex of adult animals. Our results indicate that MatSep can selectively modify the intracellular protein degradation machinery in ways that may impact the development and progression of neurodegenerative disease.

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Section: Discussionsupporting

confidence: 93%

Neonatal Maternal Separation Modifies Proteostasis Marker Expression in the Adult Hippocampus

Sierra-Fonseca

Hamdan

Cohen

et al. 2021

Front. Mol. Neurosci.

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“…The higher frailty among the adoptees may thus reflect early life stress, caused by being separated from one’s biological family. A similar finding on childhood stress and frailty was recently reported in the Helsinki Birth Cohort Study; those men who were evacuated abroad unaccompanied by their parents in childhood during World War II had a higher risk of frailty (measured using the FP) in late life compared to nonseparated men ( 35 ). However, the Finnish study found no associations in women.…”

Section: Discussionsupporting

confidence: 81%

Drivers of Frailty from Adulthood into Old Age: Results from a 27-Year Longitudinal Population-Based Study in Sweden

Raymond

Reynolds

Aslan

et al. 2020

The Journals of Gerontology: Series A

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Background Frailty is a strong predictor of adverse outcomes. However, longitudinal drivers of frailty are not well understood. This study aimed at investigating the longitudinal trajectories of a frailty index (FI) from adulthood to late life and identifying the factors associated with the level and rate of change in FI. Methods An age-based latent growth curve analysis was performed in the Swedish Adoption/Twin Study of Aging (N = 1,842; aged 29–102 years) using data from up to 15 measurement waves across 27 years. A 42-item FI was used to measure frailty at each wave. Results A bilinear, two-slope model with a turning point at age 65 best described the age-related change in FI, showing that the increase in frailty was more than twice as fast after age 65. Underweight, obesity, female sex, overweight, being separated from one’s co-twin during childhood, smoking, poor social support, and low physical activity were associated with a higher FI at age 65, with underweight having the largest effect size. When tested as time-varying covariates, underweight and higher social support were associated with a steeper increase in FI before age 65, whereas overweight and obesity were associated with less steep increase in FI after age 65. Conclusions Factors associated with the level and rate of change in frailty are largely actionable and could provide targets for intervention. As deviations from normal weight showed the strongest associations with frailty, future public health programs could benefit from monitoring of individuals with abnormal BMI, especially those who are underweight.

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“…The higher FI among the adoptees may thus reflect early life stress, caused by being separated from one's biological family. A similar finding on childhood stress and frailty was recently reported in the Helsinki Birth Cohort Study; those men who were evacuated abroad unaccompanied by their parents in childhood during World War II had a higher risk of frailty (measured using the FP) in late life compared to non-separated men (29). However, this study found no associations in women.…”

Section: Discussionsupporting

confidence: 88%

Drivers of Frailty from Adulthood into Old Age: Results from a 27-year Longitudinal Population-Based Study in Sweden

Raymond

Reynolds

Aslan

et al. 2019

Preprint

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Background. Frailty is a strong predictor of adverse aging outcomes. However, the longitudinal drivers of frailty are not well understood. This study aimed at investigating the longitudinal trajectories of a frailty index (FI) from adulthood to late life and identifying the predictors of the level and rate of change in FI. Methods. An age-based latent growth curve analysis was performed in the Swedish Adoption/Twin Study of Aging (N=1,842; aged 29-102 years) using data from up to 15 measurement waves across 27 years. A 42-item FI was used to measure frailty at each wave. Results. A bilinear, two-slope model with a turning point at age 65 best described the age-related change in FI, showing that the rate of increase in frailty was more than twice as fast after age 65. Underweight, obesity, female sex, overweight, being separated from one's co-twin during childhood, smoking, poor social support and low physical activity were associated with a higher level of FI at age 65, with underweight having the largest effect size. When tested as time-varying predictors, underweight and higher social support were associated with a steeper increase in FI before age 65, whereas overweight and obesity were associated with less steep increase in FI after age 65. Conclusions. Predictors for the level and rate of change in frailty are largely actionable and could provide targets for intervention. Underweight increased the risk of higher FI trajectory until age 65, whereas being overweight or obese were associated with slower progression of frailty towards the oldest ages.

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Early life stress and frailty in old age: the Helsinki birth cohort study

Cited by 32 publications

References 36 publications

Neonatal Maternal Separation Modifies Proteostasis Marker Expression in the Adult Hippocampus

Neonatal Maternal Separation Modifies Proteostasis Marker Expression in the Adult Hippocampus

Drivers of Frailty from Adulthood into Old Age: Results from a 27-Year Longitudinal Population-Based Study in Sweden

Drivers of Frailty from Adulthood into Old Age: Results from a 27-year Longitudinal Population-Based Study in Sweden

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