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Hormone-sensitive lipase works in the nucleus to keep fat cells healthy, new study suggests

In Alzheimer's disease (AD), hyperactivated microglia produce inflammatory mediators that contribute to neuroinflammation and neuronal damage. Amyloid precursor protein (APP), a transmembrane protein expressed in many cell types, including neurons and microglia, plays a critical role in AD pathogenesis via its secretase-mediated processing to release the C-terminal 99-residue transmembrane fragment (C99) that is further cleaved to yield amyloid-β peptides. Voltage-gated proton channels (Hv1)...

Lamin A/C (LMNA), a key component of the nuclear envelope, is essential for maintaining nuclear integrity and genome organization [W. Xie et al., Curr. Biol. 26, 2651-2658 (2016)]. While LMNA dysregulation has been implicated in genomic instability across cancer and aging, the underlying mechanisms remain poorly understood [S. Graziano et al., Nucleus 9, 258-275 (2018)]. Here, we define a mechanistic role for LMNA in preserving genome stability in small-cell lung cancer (SCLC), a malignancy...

In multicellular organisms, sensory perception affects many aspects of behavior and physiology. Perception of environmental stressors like food scarcity often leads to physiological changes that promote survival and slow aging. However, recent work shows that perception of attractive food smells can block the health benefits of dietary restriction in multiple model organisms. While it is known that sensory perception and cell nonautonomous signaling can modulate health and longevity, our...

CONCLUSION: The study offers insights into early detection and prevention strategies for healthy aging. Assuming that physical and cognitive domains are primarily driven by age-related biological changes, our findings support theories proposing that biological changes precede functional decline, and theories emphasizing the importance of psychosocial resilience. Moreover, this study highlights the potential of adopting a complex systems approach and innovative within-person analytical methods in...

CONCLUSION: This study highlights the heterogeneity of functional transitions during the aging process. Within this cohort, orientation emerged as the most consistent protective factor against functional deterioration. The protective role of orientation is likely attributable not only to its fundamental importance for performing essential functional tasks, but also as a key early indicator of mild cognitive impairment and dementia. These findings underscore that distinct cognitive predictors can...

CONCLUSIONS: Following hospitalization for stroke and hip fracture, discharge to an IRF was associated with lower mortality relative to SNF. However, given the potential for unmeasured confounding, this association should be interpreted with caution. Careful post-acute care referral protocols are critical to ensure good patient outcomes.

p53 is a key tumor suppressor, and mutations in the p53 gene occur in more than half of all human cancers. p53, which is under tight and complex regulation in cells, functions primarily as a transcription factor regulating genes involved in many cellular processes, including cell cycle arrest, apoptosis, senescence, ferroptosis, and metabolism, thereby maintaining genomic integrity and preventing tumorigenesis. While the cell-intrinsic functions of p53, which contribute to its tumor-suppressive...

A decline in food-searching behavior of post-reproductive animals can benefit the population and possibly be programmed by the genome despite its detrimental effect on an individual. We investigated the genetic program of age-dependent decline in chemotaxis behavior toward an odorant secreted from bacterial food in C. elegans. Through a novel forward genetic screen, we identified the gene encoding a nuclear hormone receptor, nhr-76, whose mutants ameliorate the age-dependent chemotaxis decline....

Parkinson disease (PD) and other α-synucleinopathies are characterized by the intracellular aggregates of SNCA/α-synuclein (synuclein, alpha) thought to spread via cell-to-cell transmission. To understand the contributions of various brain cells to the spreading of SNCA pathology, we examined the metabolism of SNCA aggregates in neuronal and glial cells. In neurons, while the full-length SNCA rapidly disappeared following SNCA pre-formed-fibril (PFF) uptake, truncated SNCA accumulated with a...

Science, Volume 390, Issue 6771, October 2025.

Science, Volume 390, Issue 6771, October 2025.

Science, Volume 390, Issue 6771, October 2025.

Science, Volume 390, Issue 6771, October 2025.

Science, Volume 390, Issue 6771, October 2025.

Science, Volume 390, Issue 6771, October 2025.

Science, Volume 390, Issue 6771, October 2025.

Science, Volume 390, Issue 6771, October 2025.