Next, we used Mendelian randomization to test the causal influence of sleep on aging We didn't find evidence that self-reported insomnia causes faster aging (top panels), but we did find evidence that a formal diagnosis of a sleep disorder (organic or nonorganic) causes faster aging (bottom panels)

But does this mean sleeping badly causes us to age faster? We first tried to get closer to this question with two datasets of twins to control for shared genetics and early environment. When comparing twins from both datasets, the correlation between sleep and aging was much less convincing.

Across all five datasets (total N > 64,000), sleeping poorly was correlated with faster aging. This was true among 18-year-olds, people in their 90s, with epigenetic and neuroimaging pace-of-aging biomarkers, and after accounting for the presence of chronic diseases.

Crucially, the effects for DunedinPACNI were largely non-overlapping with brain age gap, suggesting that these measures capture unique aspects of aging in schizophrenia

We recently introduced such a measure - DunedinPACNI. This measure leverages longitudinal measurement of aging from the Dunedin Study, a birth cohort now in midlife, to enhance the measurement of aging www.nature.com/articles/s43...

Is schizophrenia associated with accelerated aging? In our new paper, we find evidence for consistently faster aging in schizophrenia, though not among unaffected siblings nor clinical high-risk youth doi.org/10.1017/S003...

DunedinPACNI tended to explain a bit more variance in clinical outcomes. Notably, this variance did not overlap with brain age gap very much and DunedinPACNI and brain age gap were not very correlated.

DunedinPACNI’s association with cognitive impairment in BrainLat was similar to that in ADNI, an initial indication of good generalization among people from Latin America.

In UK Biobank, faster DunedinPACNI scores were related to frailty, number of chronic illnesses, risk of new chronic illness, and risk of death from any cause. Thus, DunedinPACNI appears to index aging across the entire body

Furthermore, faster DunedinPACNI scores at baseline predicted more rapid hippocampal atrophy in the future.

In ADNI and UK Biobank, faster DunedinPACNI scores were correlated with worse cognition, cognitive impairment, and risk of cognitive decline

Using Dunedin Study data, we trained an algorithm to estimate the Pace of Aging from brain structure. We call this measure “DunedinPACNI” – Pace of Aging Calculated from NeuroImaging Then we applied this algorithm to external data to test its association with clinical outcomes.

We averaged the decline in each of these biomarkers to get a summary score of whole-body aging called “Pace of Aging”