bims-minfam 2024-12-01 papers

Issue of 2024–12–01
five papers selected by
Ayesh Seneviratne, McMaster University

Nat Aging. 2024 Nov 27.

Late-life protein or isoleucine restriction impacts physiological and molecular signatures of aging.

Chung-Yang Yeh, Lucas C S Chini, Jessica W Davidson, Gonzalo G Garcia, Meredith S Gallagher, Isaac T Freichels, Mariah F Calubag, Allison C Rodgers, Cara L Green, Reji Babygirija, Michelle M Sonsalla, Heidi H Pak, Michaela E Trautman, Timothy A Hacker, Richard A Miller, Judith A Simcox, Dudley W Lamming.

Restricting the intake of protein or the branched-chain amino acid isoleucine promotes healthspan and extends lifespan in young or adult mice. However, their effects when initiated in aged animals are unknown. Here we investigate the consequences of consuming a diet with 67% reduction of all amino acids (low AA) or of isoleucine alone (low Ile), in male and female C57BL/6J.Nia mice starting at 20 months of age. Both dietary regimens effectively promote overall metabolic health without reducing calorie intake. Both low AA and low Ile diets improve aspects of frailty and slow multiple molecular indicators of aging rate; however, the low Ile diet reduces grip strength in both sexes and has mixed, sexually dimorphic effects on the heart. These results demonstrate that low AA and low Ile diets can promote aspects of healthy aging in aged mice and suggest that similar interventions might promote healthy aging in older adults.

DOI: https://doi.org/10.1038/s43587-024-00744-7

Nat Commun. 2024 Nov 26. 15(1): 10268

Developmental hematopoietic stem cell variation explains clonal hematopoiesis later in life.

Jesse Kreger, Jazlyn A Mooney, Darryl Shibata, Adam L MacLean.

Clonal hematopoiesis becomes increasingly common with age, but its cause is enigmatic because driver mutations are often absent. Serial observations infer weak selection indicating variants are acquired much earlier in life with unexplained initial growth spurts. Here we use fluctuating CpG methylation as a lineage marker to track stem cell clonal dynamics of hematopoiesis. We show, via the shared prenatal circulation of monozygotic twins, that weak selection conferred by stem cell variation created before birth can reliably yield clonal hematopoiesis later in life. Theory indicates weak selection will lead to dominance given enough time and large enough population sizes. Human hematopoiesis satisfies both these conditions. Stochastic loss of weakly selected variants is naturally prevented by the expansion of stem cell lineages during development. The dominance of stem cell clones created before birth is supported by blood fluctuating CpG methylation patterns that exhibit low correlation between unrelated individuals but are highly correlated between many elderly monozygotic twins. Therefore, clonal hematopoiesis driven by weak selection in later life appears to reflect variation created before birth.

DOI: https://doi.org/10.1038/s41467-024-54711-2

Front Endocrinol (Lausanne). 2024 ;15 1424826

Mitochondria: the epigenetic regulators of ovarian aging and longevity.

Shalini Mani, Vidushi Srivastava, Chesta Shandilya, Aditi Kaushik, Keshav K Singh.

Ovarian aging is a major health concern for women. Ovarian aging is associated with reduced health span and longevity. Mitochondrial dysfunction is one of the hallmarks of ovarian aging. In addition to providing oocytes with optimal energy, the mitochondria provide a co-substrate that drives epigenetic processes. Studies show epigenetic alterations, both nuclear and mitochondrial contribute to ovarian aging. Both, nuclear and mitochondrial genomes cross-talk with each other, resulting in two ways orchestrated anterograde and retrograde response that involves epigenetic changes in nuclear and mitochondrial compartments. Epigenetic alterations causing changes in metabolism impact ovarian function. Key mitochondrial co-substrate includes acetyl CoA, NAD+, ATP, and α-KG. Thus, enhancing mitochondrial function in aging ovaries may preserve ovarian function and can lead to ovarian longevity and reproductive and better health outcomes in women. This article describes the role of mitochondria-led epigenetics involved in ovarian aging and discusses strategies to restore epigenetic reprogramming in oocytes by preserving, protecting, or promoting mitochondrial function.

Keywords: aging; epigenetics; menopause; mitochondria; ovary

DOI: https://doi.org/10.3389/fendo.2024.1424826