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International audience; Gene-transfer methods are useful to study the structural or functional roles of recombinant proteins in vitro. In particular, adenovirus-mediated gene transduction results in strong efficiency and high level of expression in primary cells such as cardiomyocytes, which are difficult to transfect with classical methods. Here, we describe a protocol that enables efficient expression of MAO A in both primary cells and cell lines. Following expression of recombinant MAO A, substrate-induced activation of the enzyme can be assessed by measuring production of reactive oxygen species and downstream signal transduction pathways in cells. This model allows to decipher the biological function of MAO A on metabolism, mitochondrial fitness, cell death/survival, and proliferation.

Background Growth differentiation factor 15 (GDF15) has been associated with several age-related disorders, but its associations with functional abilities in community-dwelling older adults are not well studied. Methods The study was a secondary analysis of 1 096 community-dwelling older adults (aged 69–94 years) recruited from the Multidomain Alzheimer’s Preventive Trial. Plasma GDF15 was measured 1 year after participants’ enrollment. Annual data of physical performance (grip strength and Short Physical Performance Battery [SPPB]) and global cognitive functions (Mini-Mental State Examination [MMSE] and a composite cognitive score) were measured for 4 years. Adjusted mixed-effects linear models were performed for cross-sectional and longitudinal association analyses. Results A higher GDF15 was cross-sectionally associated with a weaker grip strength (β = −1.1E−03, 95% CI [−2.0E−03, −1.5E−04]), a lower SPPB score (β = −3.1E−04, 95% CI [−5.4E−04, −9.0E−05]), and worse cognitive functions (β = −2.4E−04, 95% CI [−3.3E−04, −1.6E−04] for composite cognitive score; β = −4.0E−04, 95% CI [−6.4E−04, −1.6E−04] for MMSE). Participants with higher GDF15 demonstrated greater longitudinal declines in SPPB (β = −1.0E−04, 95% CI [−1.7E−04, −2.0E−05]) and composite cognitive score (β = −2.0E−05, 95% CI [−4.0E−05, −3.6E−06]). The optimal initial GDF15 cutoff values for identifying participants with minimal clinically significant decline after 1 year were 2 189 pg/mL for SPPB (AUC: 0.580) and 2 330 pg/mL for composite cognitive score (AUC: 0.587). Conclusions Plasma GDF15 is cross-sectionally and longitudinally associated with lower-limb physical performance and global cognitive function in older adults. Circulating GDF15 alone has a limited capacity of discriminating older adults who will develop clinically significant functional declines. Clinical Trial Registration NCT00672685

This study aimed to investigate the interaction between weight loss (WL) and plasma amyloid-β (42/40) (Aβ (42/40)), neurofilament light chain (NfL), progranulin, and their association with cognitive decline over time among older adults. This 5-year observational approach included 470 participants from the Multidomain Alzheimer Preventive Trial, mean age 76.8 years (SD = 4.5), 59.4% women. WL was defined as ≥5% decrease over the first year. Biomarkers were measured at 12 months. Cognitive function was assessed yearly from 12 months onward by Mini-Mental State Examination (MMSE); Clinical Dementia Rating sum of boxes (CDR-SB); a composite score based on Category Naming Test; Digit Symbol Substitution Test; 10 MMSE orientation items (MMSEO) and free and total recall of the Free and Cued Selective Reminding test; and these tests individually. Twenty-seven participants (5.7%) presented WL. In adjusted analyses, combined WL + lower Aβ (42/40) (≤0.103, lowest quartile) was related with more pronounced 4-year cognitive decline according to CDR-SB (p < .0001) and MMSEO (p = .021), compared with non-WL + higher Aβ (42/40). WL + higher NfL (>94.55 pg/mL, highest quartile) or progranulin (>38.4 ng/mL, 3 higher quartiles) were related with higher cognitive decline according to CDR-SB, MMSE, MMSEO, and composite score (all p < .03), compared with non-WL + lower NfL or higher progranulin. Regrouping progranulin quartiles (Q1–Q3 vs Q4) revealed higher cognitive decline among the WL + lower progranulin group compared with non-WL + lower progranulin. In conclusion, 1-year WL was associated with subsequent higher 4-year cognitive decline among older adults presenting low Aβ (42/40) or high NfL. Future studies combining plasma biomarker assessments and body weight surveillance may be useful for identifying people at risk of cognitive impairment. Clinical trial number: NCT00672685.

Additional file 7. Within group evolution in memory outcomes, executive function and attention according to plasma MCP-1 status (excluding ApoE ��4 genotype). Mixed-effect linear regression analysis for variation in memory outcomes over time according to plasma MCP-1 status among community-dwelling older adults (excluding ApoE ��4 genotype).

Additional file 6. Within group evolution in overall cognitive outcomes, executive function and attention according to plasma MCP-1 status (excluding ApoE ��4 genotype). Within group evolution in memory outcomes over time according to plasma MCP-1 status among community-dwelling older adults (excluding ApoE ��4 genotype).

Additional file 1. Description of features of ELLA System for plasma MCP-1 determination.

Additional file 5. Evolution in overall memory outcomes according to plasma MCP-1 status (excluding ApoE ��4 genotype). Mixed-effect linear regression analysis for variation in memory outcomes over time according to plasma MCP-1 status among community-dwelling older adults (excluding ApoE ��4 genotype).

Additional file 4. Evolution in overall cognitive outcomes, executive function and attention according to plasma MCP-1 status (excluding ApoE ��4 genotype). Mixed-effect linear regression analysis for variation in overall cognitive outcomes, executive function and attention over time according to plasma MCP-1 status among community-dwelling older adults (excluding ApoE ��4 genotype).

Additional file 2. Neuroimaging procedures. Description of neuroimaging techniques used in the present study.

Additional file 3. Differences between included and excluded participants. Differences in baseline characteristics between MAPT study participants included and excluded in the present study.

International audience; The find solutions for optimizing healthy aging and increase health span is one of the main challenges for our society. A novel healthcare model based on integration and a shift on research and care towards the maintenance of optimal functional levels are now seen as priorities by the WHO. To address this issue, an integrative global strategy mixing longitudinal and experimental cohorts with an innovative transverse understanding of physiological functioning is missing. While the current approach to the biology of aging is mainly focused on parenchymal cells, we propose that age-related loss of function is largely determined by three elements which constitute the general ground supporting the different specific parenchyma: i.e. the stroma, the immune system and metabolism. Such strategy that is implemented in INSPIRE projects can strongly help to find a composite biomarker capable of predicting changes in capacity across the life course with thresholds signalling frailty and care dependence.