bims-minfam 2023-08-27 papers

Issue of 2023–08–27
seven papers selected by
Ayesh Seneviratne, Western University

Nat Commun. 2023 Aug 19. 14(1): 5038

Challenges in developing Geroscience trials.

G.C.T-TF group

Geroscience is becoming a major hope for preventing age-related diseases and loss of function by targeting biological mechanisms of aging. This unprecedented paradigm shift requires optimizing the design of future clinical studies related to aging in humans. Researchers will face a number of challenges, including ideal populations to study, which lifestyle and Gerotherapeutic interventions to test initially, selecting key primary and secondary outcomes of such clinical trials, and which age-related biomarkers are most valuable for both selecting interventions and predicting or monitoring clinical responses ("Gerodiagnostics"). This article reports the main results of a Task Force of experts in Geroscience.

DOI: https://doi.org/10.1038/s41467-023-39786-7

Aging (Albany NY). 2023 Aug 22. undefined

Mitochondria: between aging, frailty and sarcopenia.

Annalisa Davin, Riccardo Rocco Ferrari, Orietta Pansarasa.

Keywords: biomarkers; frailty; mitochondrial dysfunction; mtDNA; sarcopenia

DOI: https://doi.org/10.18632/aging.204998

Nutrients. 2023 Aug 21. pii: 3660. [Epub ahead of print]15(16):

Short-Term Caloric Restriction and Subsequent Re-Feeding Compromise Liver Health and Associated Lipid Mediator Signaling in Aged Mice.

Patrick Schädel, Mareike Wichmann-Costaganna, Anna Czapka, Nadja Gebert, Alessandro Ori, Oliver Werz.

Aging is characterized by alterations in the inflammatory microenvironment, which is tightly regulated by a complex network of inflammatory mediators. Excessive calorie consumption contributes to age- and lifestyle-associated diseases like obesity, type 2 diabetes, cardiovascular disorders, and cancer, while limited nutrient availability may lead to systemic health-promoting adaptations. Geroprotective effects of short-term caloric restriction (CR) can beneficially regulate innate immune receptors and interferon signaling in the liver of aged mice, but how CR impacts the hepatic release of immunomodulatory mediators like cytokines and lipid mediators (LM) is elusive. Here, we investigated the impact of aging on the inflammatory microenvironment in the liver and its linkage to calorie consumption. The livers of female young and aged C57BL/6JRj mice, as well as of aged mice after caloric restriction (CR) up to 28 days, with and without subsequent re-feeding (2 days), were evaluated. Surprisingly, despite differences in the hepatic proteome of young and old mice, aging did not promote a pro-inflammatory environment in the liver, but it reduced lipoxygenase-mediated formation of LM from polyunsaturated fatty acids without affecting the expression of the involved lipoxygenases and related oxygenases. Moreover, CR failed to ameliorate the secretion of pro-inflammatory cytokines but shifted the LM production to the formation of monohydroxylated LM with inflammation-resolving features. Unexpectedly, re-feeding after CR even further decreased the inflammatory response as LM species were markedly downregulated. Our findings raise the question of how short-term CR is indeed beneficial as a nutritional intervention for healthy elderly subjects and further stress the necessity to address tissue-specific inflammatory states.

Keywords: PUFA metabolism; aging; caloric restriction; inflammation; lipid mediators; lipoxygenase; liver

DOI: https://doi.org/10.3390/nu15163660

J Cell Mol Med. 2023 Aug 23.

Challenges in anti-aging medicine-trends in biomarker discovery and therapeutic interventions for a healthy lifespan.

Iuliana Popescu, Joris Deelen, Maddalena Illario, Jan Adams.

We are facing a growing aging population, along with increasing pressure on health systems, caused by the impact of chronic co-morbidities (i.e. cancer, cardiovascular and neurodegenerative diseases) and functional disabilities as people age. Relatively simple preventive lifestyle interventions, such as dietary restriction and physical exercise, are important contributors to active and healthy aging in the general population. However, as shown in model organisms or in 'in vitro' conditions, lifestyle-independent interventions may have additional health benefits and can even be conceived as possible reversers of the aging process. Thus, pharmaceutical laboratories, research institutes, and universities are putting more and more effort into finding new molecular pathways and druggable targets to develop gerotherapeutics. One approach is to target the driving mechanisms of aging, some of which, like cellular senescence and impaired autophagy, we discussed in an update on the biology of aging at AgingFit 2023 in Lille, France. We underline the importance of carefully and extensively testing senotherapeutics, given the pleiotropism and heterogeneity of targeted senescent cells within different organs, at different time frames. Other druggable targets emerging from new putative mechanisms, like those based on transcriptome imbalance, nucleophagy, protein phosphatase depletion, glutamine metabolism, or seno-antigenicity, have been evidenced by recent preclinical studies in classical models of aging but need to be validated in humans. Finally, we highlight several approaches in the discovery of biomarkers of healthy aging, as well as for the prediction of neurodegenerative diseases and the evaluation of rejuvenation strategies.

Keywords: autophagy; biomarkers; centenarians; inflammaging; lifespan; lifestyles; rejuvenation; senescence; senolytics; senomorphics

DOI: https://doi.org/10.1111/jcmm.17912