Search bioRxiv⌕ Search

Biology subjects

Hulmi, J. J.

Publications and source records attributed to Hulmi, J. J..

2 recordsLinked to original sources

Age but not menopausal status is linked to lower resting energy expenditure

ContextIt remains uncertain whether aging before late adulthood and menopause are associated with fat-free mass and fat mass-adjusted resting energy expenditure (REEadj). ObjectivesWe investigated whether REEadj differs between middle-aged and younger women and between middle-aged women with different menopausal statuses. We repeated the age group comparison between middle-aged mothers and their daughters to partially control for genotype. We also explored whether serum estradiol and follicle-stimulating hormone concentrations explain REEadj in midlife. MethodsWe divided 120 women, including 16 mother-daughter pairs, into age groups; group I (n = 26) consisted of participants aged 17-21, group II (n = 35) of those aged 22-38 and group III (n = 59) of those aged 41-58 years. The women in group III were further categorized as pre- or perimenopausal (n = 19), postmenopausal (n = 30) or postmenopausal hormone therapy users (n = 10). REE was assessed using indirect calorimetry, body composition using dual-energy X-ray absorptiometry and hormones using immunoassays. ResultsThe REEadj of group I was 126 kcal/d (95% CI: 93-160) higher than that of group III, and the REEadj of group II was 88 kcal/d (95% CI: 49-127) higher. Furthermore, daughters had a 100 kcal/d (95% CI: 63-138 kcal/d) higher REEadj than their middle-aged mothers (all P < 0.001). In group III, REEadj was not lower in postmenopausal women and did not vary by sex hormone concentrations. ConclusionsWe demonstrated that REEadj declines with age in women before late adulthood, also when controlling partially for genetic background, and that menopause may not contribute to this decline.

physiology↗

NAD+ repletion with niacin counteracts cancer cachexia

Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD+) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirmed that depletion of NAD+ and downregulation of Nrk2, an NAD+ biosynthetic enzyme, are common features of different mouse models and cachectic cancer patients. Testing NAD+ repletion therapy in cachectic mice revealed that NAD+ precursor, vitamin B3 niacin, efficiently corrected tissue NAD+ levels, improved mitochondrial metabolism and ameliorated cancer- and chemotherapy-induced cachexia. To examine NAD+ metabolism in a clinical setting, we showed that the low expression of NRK2 in cancer patients correlated with metabolic abnormalities underscoring the significance of NAD+ in the pathophysiology of human cancer cachexia. Overall, our results propose a novel therapy target, NAD+ metabolism, for cachectic cancer patients.

molecular biology↗