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Serum from Older Adults Increases Apoptosis and Molecular Aging Markers in Human Hippocampal Progenitor Cells.

ABSTRACT: Age-related alteration in neural stem cell function is linked to neurodegenerative conditions and cognitive decline. In rodents, this can be reversed by exposure to a young systemic milieu and conversely, the old milieu can inhibit stem cell function in young rodents. In this study, we investigated the in vitro effect of the human systemic milieu on human hippocampal progenitor cells (HPCs) using human serum from early adulthood, mid-life and older age. We showed that neuroblast number following serum treatment is predictive of larger dentate gyrus, CA3, CA4 and whole hippocampus volumes and that allogeneic human serum from asymptomatic older individuals induced a two-fold increase in apoptotic cell death of HPCs compared with serum from young adults. General linear models revealed that variability in markers of proliferation and differentiation was partly attributable to use of antihypertensive medication and very mild cognitive decline among older subjects. Finally, using an endophenotype approach and whole-genome expression arrays, we showed upregulation of established and novel ageing molecular hallmarks in response to old serum. Serum from older subjects induced a wide range of cellular and molecular phenotypes, likely reflecting a lifetime of environmental exposures. Our findings support a role for the systemic enviroment in neural stem cell maintenance and are in line with others highlighting a distinction between neurobiological and chronological ageing. Finally, the herein described serum assay can be used by future studies to further analyse the effect of environmental exposures as well as to determine the role of the systemic environment in health and disease.

SUBMITTER: de Lucia C

PROVIDER: S-EPMC8612606 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Population aging is escalating in numerous countries worldwide; among them is Taiwan, which will soon become an aged society. Thus, aging successfully is an increasing concern. One of the factors for achieving successful aging (SA) is maintaining high physical function. The purpose of this study was to determine the physical fitness factors associated with SA in Taiwanese older adults (OAs), because these factors are intervenable. Community-dwelling OAs aged more than 65 years and residing in Northern Taiwan were recruited in this study. They received a comprehensive geriatric assessment, which includes sociodemographic data, health conditions and behaviors, activities of daily living (ADL) and instrumental ADL (IADL) function, cognitive and depressive status, and quality of life. Physical fitness tests included the grip strength (GS), 30-second sit-to-stand (30s STS), timed up-and-go (TUG), functional reach (FR), one-leg standing, chair sit-and-reach, and reaction time (drop ruler) tests as well as the 6-minute walk test (6MWT). SA status was defined as follows: complete independence in performing ADL and IADL, satisfactory cognitive status (Mini-Mental State Examination ≥ 24), no depression (Geriatric Depression Scale < 5), and favorable social function (SF subscale ≥ 80 in SF-36). Adjusted multiple logistic regression analyses were performed. Among the total recruited OAs (n = 378), 100 (26.5%) met the aforementioned SA criteria. After adjustment for sociodemographic characteristics and health condition and behaviors, some physical fitness tests, namely GS, 30s STS, 6MWT, TUG, and FR tests, were significantly associated with SA individually, but not in the multivariate model. Among the physical fitness variables tested, cardiopulmonary endurance, mobility, muscle strength, and balance were significantly associated with SA in Taiwanese OAs. Early detection of deterioration in the identified functions and corresponding intervention is essential to ensuring SA.

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Serum from Older Adults Increases Apoptosis and Molecular Aging Markers in Human Hippocampal Progenitor Cells.

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