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The evolutionary biology of aging is fundamental to understanding the mechanisms of aging and how to develop anti-aging treatments. Thus far most evolutionary theory concerns the genetics of aging with limited physiological integration. Here we present an intuitive evolutionary framework built on how physiology is regulated and how this regulation itself ages. Life has evolved to secure reproduction and avoid system failure in early life, and it is the regulation that evolves in response to...

Yu and colleagues¹ demonstrate that α-synuclein pathology within the dorsal motor nucleus of the vagus (DMV) compromises neuronal excitability and drives Parkinson's disease-related gastrointestinal dysmotility through alteration of a fundamental DMV-gut circuit. Electroacupuncture reactivates this circuit ameliorating this functional deficit.

Skeletal muscle stem cells (MuSC) are the guardians of muscle regeneration, sustaining tissue integrity through a delicate balance of quiescence, activation, and lineage commitment. While numerous molecular cues have been implicated in regulating these processes, the influence of androgen receptor (AR) signaling, an essential hormonal pathway for male muscle physiology, has remained largely unexplored. Here, we show that AR expression defines quiescent MuSC and acts as a safeguard of their...

Proteins generally begin with methionine, which is often removed to expose the second residue. RuBP carboxylase/oxygenase (Rubisco), the most abundant enzyme on Earth and a major carbon and nitrogen reservoir, escapes this paradigm. Its catalytic subunit, RbcL, undergoes unusual amino terminal maturation, including atypical initiator methionine-serine cleavage and proline acetylation, a modification not seen in other biological systems. We define a specialized pathway of two sequential...

ObjectiveThis study examines how life expectancy (LE) without and with depression differs by living arrangement among older adults in Japan, with particular attention to gender differences.MethodsData were drawn from the Nihon University Japanese Longitudinal Study of Aging (1999-2009). Multistate life table methods were used to estimate LE spent without and with depression among adults aged 65 years and older across different living arrangements.ResultsPronounced gender differences were...

This year's Lasker~Bloomberg Public Service Award honors the singular achievement of Michael J. Fox, who has devoted much of his life to a philanthropic effort to conquer Parkinson's Disease (PD), a progressive neurodegenerative disorder that afflicts many millions of patients world-wide. Just a few years after his diagnosis of PD at the tender age of 29, Fox pivoted in part from his enormous success in acting [leading roles in the Back to the Future trilogy (1985-1989) and in the hit National...

Limbal niche cells (LNCs) serve as essential regulators of limbal microenvironmental homeostasis and corneal epithelial wound repair, representing a promising therapeutic resource for limbal stem cell deficiency (LSCD). However, their clinical application is constrained by replicative aging during in vitro expansion. In this study, we investigated whether a three-dimensional (3D) Matrigel-based culture system could modulate replicative aging in LNCs. Compared with conventional two-dimensional...

Bone marrow-derived macrophages were shown to play an important role in coping with Alzheimer's disease (AD). Boosting their spontaneous recruitment reduces inflammation and disease pathology and slows cognitive decline in mouse models of amyloidosis. However, the factors limiting their spontaneous homing to the diseased brain remain unclear. In this study, we discovered that monocyte development is impaired in mouse models and in patients. In the 5×FAD mouse model, monocyte differentiation was...

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