bims-minfam 2022-11-06 papers

Issue of 2022–11–06
five papers selected by
Ayesh Seneviratne, Western University

Future Healthc J. 2022 Jul;9(Suppl 2): 51

DOI: https://doi.org/10.7861/fhj.9-2-s51

Front Aging. 2022 ;3 1005322

The use of progeroid DNA repair-deficient mice for assessing anti-aging compounds, illustrating the benefits of nicotinamide riboside.

María B Birkisdóttir, Ivar van Galen, Renata M C Brandt, Sander Barnhoorn, Nicole van Vliet, Claire van Dijk, Bhawani Nagarajah, Sandra Imholz, Conny T van Oostrom, Erwin Reiling, Ákos Gyenis, Pier G Mastroberardino, Dick Jaarsma, Harry van Steeg, Jan H J Hoeijmakers, Martijn E T Dollé, Wilbert P Vermeij.

Despite efficient repair, DNA damage inevitably accumulates with time affecting proper cell function and viability, thereby driving systemic aging. Interventions that either prevent DNA damage or enhance DNA repair are thus likely to extend health- and lifespan across species. However, effective genome-protecting compounds are largely lacking. Here, we use Ercc1 Δ/- and Xpg -/- DNA repair-deficient mutants as two bona fide accelerated aging mouse models to test propitious anti-aging pharmaceutical interventions. Ercc1 Δ/- and Xpg -/- mice show shortened lifespan with accelerated aging across numerous organs and tissues. Previously, we demonstrated that a well-established anti-aging intervention, dietary restriction, reduced DNA damage, and dramatically improved healthspan, strongly extended lifespan, and delayed all aging pathology investigated. Here, we further utilize the short lifespan and early onset of signs of neurological degeneration in Ercc1 Δ/- and Xpg -/- mice to test compounds that influence nutrient sensing (metformin, acarbose, resveratrol), inflammation (aspirin, ibuprofen), mitochondrial processes (idebenone, sodium nitrate, dichloroacetate), glucose homeostasis (trehalose, GlcNAc) and nicotinamide adenine dinucleotide (NAD+) metabolism. While some of the compounds have shown anti-aging features in WT animals, most of them failed to significantly alter lifespan or features of neurodegeneration of our mice. The two NAD+ precursors; nicotinamide riboside (NR) and nicotinic acid (NA), did however induce benefits, consistent with the role of NAD+ in facilitating DNA damage repair. Together, our results illustrate the applicability of short-lived repair mutants for systematic screening of anti-aging interventions capable of reducing DNA damage accumulation.

Keywords: DNA damage repair; NAD; aging; anti-aging interventions; dietary restriction mimetics; pharmacological screening; progeria

DOI: https://doi.org/10.3389/fragi.2022.1005322

Nat Rev Rheumatol. 2022 Nov 03.

Ghada Alsaleh, Felix C Richter, Anna K Simon.

Ageing is characterized by a progressive loss of cellular function that leads to a decline in tissue homeostasis, increased vulnerability and adverse health outcomes. Important advances in ageing research have now identified a set of nine candidate hallmarks that are generally considered to contribute to the ageing process and that together determine the ageing phenotype, which is the clinical manifestation of age-related dysfunction in chronic diseases. Although most rheumatic diseases are not yet considered to be age related, available evidence increasingly emphasizes the prevalence of ageing hallmarks in these chronic diseases. On the basis of the current evidence relating to the molecular and cellular ageing pathways involved in rheumatic diseases, we propose that these diseases share a number of features that are observed in ageing, and that they can therefore be considered to be diseases of premature or accelerated ageing. Although more data are needed to clarify whether accelerated ageing drives the development of rheumatic diseases or whether it results from the chronic inflammatory environment, central components of age-related pathways are currently being targeted in clinical trials and may provide a new avenue of therapeutic intervention for patients with rheumatic diseases.

DOI: https://doi.org/10.1038/s41584-022-00863-8

Biogerontology. 2022 Oct 31.

Metabolic and physical function are improved with lifelong 15% calorie restriction in aging male mice.

Emily C Peters, Luke Safayan, Tyler J Marx, Emily Ngu, Anastasiia Vasileva, India Zappia, William H Powell, Frank A Duca, Jennifer H Stern.

Chronic calorie restriction (CR) results in lengthened lifespan and reduced disease risk. Many previous studies have implemented 30-40% calorie restriction to investigate these benefits. The goal of our study was to investigate the effects of calorie restriction, beginning at 4 months of age, on metabolic and physical changes induced by aging. Male C57BL/6NCrl calorie restricted and ad libitum fed control mice were obtained from the National Institute on Aging (NIA) and studied at 10, 18, 26, and 28 months of age to better understand the metabolic changes that occur in response to CR in middle age and advanced age. Food intake was measured in ad libitum fed controls to assess the true degree of CR (15%) in these mice. We found that 15% CR decreased body mass and liver triglyceride content, improved oral glucose clearance, and increased all limb grip strength in 10- and 18-month-old mice. Glucose clearance in ad libitum fed 26- and 28-month-old mice is enhanced relative to younger mice but was not further improved by CR. CR decreased basal insulin concentrations in all age groups and improved insulin sensitivity and rotarod time to fall in 28-month-old mice. The results of our study demonstrate that even a modest reduction (15%) in caloric intake may improve metabolic and physical health. Thus, moderate calorie restriction may be a dietary intervention to promote healthy aging with improved likelihood for adherence in human populations.

Keywords: Calorie restriction; Glucose homeostasis; Healthspan; Insulin sensitivity; Liver fat

DOI: https://doi.org/10.1007/s10522-022-09996-5