Aging & Longevity

Aging is a major risk factor for diabetic kidney disease (DKD), with both conditions exhibiting similar renal pathology. We identify the energy-sensing molecule Retinoic acid-related orphan receptor γ (RORγ) as significantly downregulated in diabetic and aged kidneys. Tubule-specific RORγ deficiency exacerbates kidney injury, whereas its overexpression protects. Mechanistically, RORγ stabilizes insulin-induced gene 1 (INSIG1) by upregulating the deubiquitinase YOD1 and enhancing AMPK activity...

Skeletal muscle aging causes loss of both muscle mss and strength, often leading to sarcopenia. Clinical manifestation of sarcopenia has been found to improve with exercise intervention. The molecular mechanisms in response to exercise intervention in aged skeletal muscles are not fully understood. We performed transcriptomic profiling of aged animal model with exercise intervention for identifying the plausible mechanism leading to enhanced muscle function. Expression levels of 43,629 RNAs were...

We leveraged allele frequencies from gnomAD, Regeneron Genetics Center Million Exome and Turkish Variome for 4591 disease genes from PanelApp and OMIM, and identified 97,135 pathogenic and 478,263 likely pathogenic variants using an American College of Medical Genetics and Genomics-based classifier. This expanded pathogenic and likely pathogenic variants nearly six-fold. On average, an individual is born with 4.70 pathogenic or likely pathogenic variants, of which 1.66 are compatible with a...

Cellular senescence is an evolutionarily conserved stress response that contributes to tissue repair and tumor suppression, yet its accumulation is also linked to aging and disease. Whether physiological senescence can be exploited by oncogenic events to promote tumorigenesis is unknown. Postpartum mammary gland involution is a major adult tissue remodeling event, resembling wound healing, and is closely associated with postpartum breast cancer. Here, we show that during mammary gland involution...

The global rise in life expectancy underscores the urgent need to extend healthspan and prevent age-related diseases. Cardiovascular disease is the leading cause of death worldwide, with ageing as a major non-modifiable risk factor. Ageing drives progressive vascular dysfunction and cardiac decline, including heart failure with preserved or reduced ejection fraction. Vascular cells are particularly vulnerable to ageing, resulting in structural and functional deterioration of the microvasculature...

Long-term preservation of digital information is vital for safeguarding the knowledge of humanity for future generations. Existing archival storage solutions, such as magnetic tapes and hard disk drives, suffer from limited media lifespans that render them unsuitable for long-term data retention^(1-3). Optical storage approaches, particularly laser writing in robust media such as glass, have emerged as promising alternatives with the potential for increased longevity. Previous work^(4-16) has...

No abstract

Amorphous materials driven away from equilibrium display a diverse repertoire of complex, history-dependent behaviors. One striking feature is a failure to return to equilibrium after an abrupt change in otherwise static external conditions. Instead, amorphous materials often exhibit physical aging: an ever-slowing, nonexponential relaxation that can span a huge range of timescales. Here, we examine the aging behavior of three different amorphous materials subjected to slow periodic driving. The...

Negative social ties, or "hasslers," are pervasive yet understudied components of social networks that may accelerate biological aging and morbidity. Using ego-centric network data and DNA methylation-based biological aging clocks (i.e., DunedinPACE and age-accelerated GrimAge2) from saliva from a state representative probability sample in Indiana, we examine how negative social ties are associated with accelerated biological aging and a broad range of health outcomes, including inflammation and...

No abstract

CONCLUSION: These findings support a relationship between declines in uneven terrain mobility and n-back cognitive function in older adults; however, this relationship was not observed in younger adults. Further research is needed to understand the shared neural mechanisms underlying age-related declines in mobility and cognitive function.

Aging is accompanied by progressive deterioration in physiological homeostasis, increasing vulnerability to metabolic, neurodegenerative, cardiovascular, and immune disorders. Over the past two decades, circadian biology has emerged as a central integrative framework linking environmental time cues to cellular, tissue, and organismal resilience. The circadian timing system (CTS), composed of a central pacemaker in the suprachiasmatic nucleus (SCN) and peripheral clocks throughout the body,...

Dementia arises from a complex interplay of biological, psychological, and sociocultural factors. However, previous large-scale studies have largely focused on biomarkers and genetics, with limited attention to the social and structural determinants of health that shape diverse aging trajectories. The Brain Resilience Study (BRS) addresses this gap by integrating multimodal biological and cognitive measures with rich demographic, psychosocial, and lifestyle data to create an open resource for...

No abstract

The proteasome is essential for cellular protein homeostasis through selective destruction of damaged and misfolded proteins. Failure of proteasome-dependent turnover accompanied by accumulation and aggregation of aberrant proteins is a hallmark of aging and late-onset neurodegenerative diseases. SKN-1A/Nrf1, a member of the NFE2L/Nrf family of transcription factors, is a master regulator of proteasome biogenesis. Through transcriptional control of proteasome subunit gene expression, SKN-1A/Nrf1...

No abstract

CONCLUSIONS: Intrinsic capacity impairment is associated with compromised HRQoL both directly and indirectly by exacerbating functional dependence. Preserving functional independence serves as a key pathway connecting intrinsic capacity to well-being. These findings highlight the imperative for integrated interventions that simultaneously bolster intrinsic capacity and support daily functional ability, tailored to diverse living environments to promote healthy aging.

An important hallmark of aging-and particularly of neurodegeneration-is the loss of proteostasis, leading to cellular stress. However, the causal mechanisms driving this loss are unclear. We show that SIRT6 has a critical role in maintaining proteostasis. Mechanistically, SIRT6 negatively regulates global translation by controlling ribosomal genes, nucleolar function and TIP5 chromatin localization. SIRT6 deletion increases nucleolar size, rRNA production and protein translation. However, the...

CONCLUSIONS: This study demonstrates that routine physical examination information could be a valuable component to incorporate into targeted assessments to screen low muscle mass among community-dwelling older adults. Building on this foundation, an interpretable machine learning approach was explored, which proves well-suited as a screening manner for low muscle mass to guide further standard assessment. Its suitability stems from superior predictive performance and operational feasibility in...

No abstract