Adipose tissue as a linchpin of organismal ageing

Nguyen, Tammy T.; Corvera, Silvia

doi:10.1038/s42255-024-01046-3

Cited by 12 publications

References 199 publications

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Injectable Gene/Fiber‐Plexes Reverse Adipose Niche Senescence via Mito‐TERT Activation by Endogenous Mitochondrial Translocation

Zhang,

He,

Ling

et al. 2024

Adv Funct Materials

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Addressing adipose niche senescence is crucial for preventing obesity‐related aging. Telomerase reverse transcriptase (TERT) is a promising target for gene therapy, but traditional methods lack precision and safety. A novel mitochondrion‐located TERT (mito‐TERT) activating approach is presented by injectable gene/short‐fiber complexes (gene/fiber‐plexes) to safely reverse adipose niche senescence from mitochondrial enhancement. The gene/fiber‐plexes are prepared from polydopamine‐coated short‐fibers to adsorb cationic dendrimers (PAMAM G3, PG3) carrying TERT plasmids and Coenzyme Q10 (CoQ10), termed PG3‐TERT@CoQ10. Upon intraperitoneal injection, the gene/fiber‐plexes adhere to the peritoneum and release PG3‐TERT@CoQ10, precisely targeting the adipose niche. Transient active oxygen scavenging by CoQ10 activates TERT transfection and endogenous mitochondrion translocation sequentially, enhancing mitochondrial function. In vitro and in vivo studies shows that gene/fiber‐plexes effectively targeted visceral adipose tissue, increased mito‐TERT levels and restored mitochondrial function. In an obese mouse model, they restored adipose tissue homeostasis and metabolic stability. RNA sequencing indicated reduced senescence‐related genes and restored cell cycle. This mito‐TERT activation strategy shows great promise for treating premature aging and metabolic diseases linked to adipose tissue senescence.

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Injectable Gene/Fiber‐Plexes Reverse Adipose Niche Senescence via Mito‐TERT Activation by Endogenous Mitochondrial Translocation

Zhang,

He,

Ling

et al. 2024

Adv Funct Materials

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Ucp1 Ablation Improves Skeletal Muscle Glycolytic Function in Aging Mice

Qiu,

Guo,

Guo

et al. 2024

Advanced Science

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Muscular atrophy is among the systematic decline in organ functions in aging, while defective thermogenic fat functionality precedes these anomalies. The potential crosstalk between adipose tissue and muscle during aging is poorly understood. In this study, it is showed that UCP1 knockout (KO) mice characterized deteriorated brown adipose tissue (BAT) function in aging, yet their glucose homeostasis is sustained and energy expenditure is increased, possibly compensated by improved inguinal adipose tissue (iWAT) and muscle functionality compared to age‐matched WT mice. To understand the potential crosstalk, RNA‐seq and metabolomic analysis were performed on adipose tissue and muscle in aging mice and revealed that creatine levels are increased both in iWAT and muscle of UCP1 KO mice. Interestingly, molecular analysis and metabolite tracing revealed that creatine biosynthesis is increased in iWAT while creatine uptake is increased in muscle in UCP1 KO mice, suggesting creatine transportation from iWAT to muscle. Importantly, creatine analog β‐GPA abolished the differences in muscle functions between aging WT and UCP1 KO mice, while UCP1 inhibitor α‐CD improved muscle glycolytic function and glucose metabolism in aging mice. Overall, these results suggested that iWAT and skeletal muscle compensate for declined BAT function during aging via creatine metabolism to sustain metabolic homeostasis.

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Effect of abdominal adipose tissue glucose uptake on brain aging

Lu,

Duan,

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONAbdominal adipose tissue (AT) mass has adverse effects on the brain. This study aimed to investigate the effect of glucose uptake by abdominal AT on brain aging.METHODSThree‐hundred twenty‐five participants underwent total‐body positron emission tomography scan. Brain age was estimated in an independent test set (n = 98) using a support vector regression model that was built using a training set (n = 227). Effects of abdominal subcutaneous and visceral AT (SAT/VAT) glucose uptake on brain age delta were evaluated using linear regression.RESULTSHigher VAT glucose uptake was linked to negative brain age delta across all subgroups. Higher SAT glucose uptake was associated with negative brain age delta in lean individuals. In contrast, increased SAT glucose uptake demonstrated positive trends with brain age delta in female and overweight/obese participants.DISCUSSIONIncreased glucose uptake of the abdominal VAT has positive influences on the brain, while SAT may not have such influences, except for lean individuals.Highlights Higher glucose uptake of the visceral adipose tissue was linked to decelerated brain aging. Higher glucose uptake of the subcutaneous adipose tissue (SAT) was associated with negative brain age delta in lean individuals. Faster brain aging was associated with increased glucose uptake of the SAT in female and overweight and obese individuals.

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Adipose tissue as a linchpin of organismal ageing

Cited by 12 publications

References 199 publications

Injectable Gene/Fiber‐Plexes Reverse Adipose Niche Senescence via Mito‐TERT Activation by Endogenous Mitochondrial Translocation

Injectable Gene/Fiber‐Plexes Reverse Adipose Niche Senescence via Mito‐TERT Activation by Endogenous Mitochondrial Translocation

Ucp1 Ablation Improves Skeletal Muscle Glycolytic Function in Aging Mice

Effect of abdominal adipose tissue glucose uptake on brain aging

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