Health and frailty among older spousal caregivers:an observational cohort study in Belgium

Abstract Background Among older couples, spouses are first in line to provide care, and they are key elements in the home support of dependent older persons. In this context, ensuring the health of these older spousal caregivers should be an important issue for all of the providers who care for older adults. The aim of this study was to longitudinally assess the health of older spousal caregivers considering frailty, nutrition, cognition, physical performance and mood disorders. Methods In this longitudinal, observational cohort study, participants were assessed at home in Wallonia, Belgium. At baseline, 82 community-dwelling spouses of older patients with cognitive deficits or functional impairment were assessed; 78 caregivers were assessed at follow-up (16 months). The clinical instruments used included Frailty Phenotype (Fried), the Mini Nutritional Assessment-short form (MNA-SF), Short Physical Performance Battery (SPPB), Geriatric Depression Scale (GDS-15), clock drawing test, medications, Zarit Burden Index (ZBI), and Caregiver Reaction Assessment (CRA). Biological assessments included plasma interleukin-6 (IL-6), ultrasensitive C-reactive protein (CRP), cortisol, albumin and insulin growth factor-1 (IGF-1). Results Among caregivers, 54% were women, and the mean age was 80 years. Among care-receivers, 83% had cognitive impairment. Caregivers were more likely to be in a pre-frail stage. In one-third of the caregivers, the frailty status worsened. Transitions were observed between each of the states, except from frail to robust. In contrast to frailty, items including nutrition, cognitive status, SPPB and mood assessments were stable over time, with approximately 70% of the caregivers not experiencing significant change at follow-up. Caregiver experiences assessed with the Zarit Burden Interview and CRA were relatively stable over 16 months. Conclusion Many caregivers of geriatric patients are spouses who are old themselves. A failure in the health of the caregiver may anticipate an undesired care breakdown. Caregiver health and its determinants should be explored in future longitudinal studies that cover a longer time period

Exploring the Communication of the SASP:Dynamic, Interactive, and Adaptive Effects on the Microenvironment

Cellular senescence is a complex cell state that can occur during physiological ageing or after exposure to stress signals, regardless of age. It is a dynamic process that continuously evolves in a context-dependent manner. Senescent cells interact with their microenvironment by producing a heterogenous and plastic secretome referred to as the senescence-associated secretory phenotype (SASP). Hence, understanding the cross-talk between SASP and the microenvironment can be challenging due to the complexity of signal exchanges. In this review, we first aim to update the definition of senescence and its associated biomarkers from its discovery to the present day. We detail the regulatory mechanisms involved in the expression of SASP at multiple levels and develop how SASP can orchestrate microenvironment modifications, by focusing on extracellular matrix modifications, neighboring cells’ fate, and intercellular communications. We present hypotheses on how these microenvironmental events may affect dynamic changes in SASP composition in return. Finally, we discuss the various existing approaches to targeting SASP and clarify what is currently known about the biological effects of these modified SASPs on the cellular environment.</p

Age-related cellular copper dynamics in the fungal ageing model Podospora anserina and in ageing human fibroblasts

In previous investigations an impact of cellular copper homeostasis on ageing of the ascomycete Podospora anserina has been demonstrated. Here we provide new data indicating that mitochondria play a major role in this process. Determination of copper in the cytosolic fraction using total reflection X-ray fluorescence spectroscopy analysis and eGfp reporter gene studies indicate an age-related increase of cytosolic copper levels. We show that components of the mitochondrial matrix (i.e. eGFP targeted to mitochondria) become released from the organelle during ageing. Decreasing the accessibility of mitochondrial copper in P. anserina via targeting a copper metallothionein to the mitochondrial matrix was found to result in a switch from a copper-dependent cytochrome-c oxidase to a copper-independent alternative oxidase type of respiration and results in lifespan extension. In addition, we demonstrate that increased copper concentrations in the culture medium lead to the appearance of senescence biomarkers in human diploid fibroblasts (HDFs). Significantly, expression of copper-regulated genes is induced during in vitro ageing in medium devoid of excess copper suggesting that cytosolic copper levels also increase during senescence of HDFs. These data suggest that the identified molecular pathway of age-dependent copper dynamics may not be restricted to P. anserina but may be conserved from lower eukaryotes to humans

UV, stress and aging

Skin is a model of choice in studies on aging. Indeed, skin aging can be modulated by internal and external factors, reflecting its complexity. Two types of skin aging have been identified: intrinsic, mainly genetically determined and extrinsic—also called "photo-aging"—resulting on the impact of environmental stress and more precisely of UV rays. Simplified in vitro models, based on cellular senescence, have been developed to study the relationship between UV and aging. These models vary on the cell type (fibroblasts or keratinocytes, normal or immortalized) and the type of UV used (UVA or UVB)

Els artistes i la guerra

Abstract not availabl

Proteomic Profiling of Human Keratinocytes Undergoing UVB-Induced Alternative Differentiation Reveals TRIpartite Motif Protein 29 as a Survival Factor

BACKGROUND: Repeated exposures to UVB of human keratinocytes lacking functional p16(INK-4a) and able to differentiate induce an alternative state of differentiation rather than stress-induced premature senescence. METHODOLOGY/PRINCIPAL FINDINGS: A 2D-DIGE proteomic profiling of this alternative state of differentiation was performed herein at various times after the exposures to UVB. Sixty-nine differentially abundant protein species were identified by mass spectrometry, many of which are involved in keratinocyte differentiation and survival. Among these protein species was TRIpartite Motif Protein 29 (TRIM29). Increased abundance of TRIM29 following UVB exposures was validated by Western blot using specific antibody and was also further analysed by immunochemistry and by RT-PCR. TRIM29 was found very abundant in keratinocytes and reconstructed epidermis. Knocking down the expression of TRIM29 by short-hairpin RNA interference decreased the viability of keratinocytes after UVB exposure. The abundance of involucrin mRNA, a marker of late differentiation, increased concomitantly. In TRIM29-knocked down reconstructed epidermis, the presence of picnotic cells revealed cell injury. Increased abundance of TRIM29 was also observed upon exposure to DNA damaging agents and PKC activation. The UVB-induced increase of TRIM29 abundance was dependent on a PKC signaling pathway, likely PKCdelta. CONCLUSIONS/SIGNIFICANCE: These findings suggest that TRIM29 allows keratinocytes to enter a protective alternative differentiation process rather than die massively after stress