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Phenotypic aging is ubiquitous across mammalian species, suggesting shared underlying mechanisms of aging. Aging is linked to molecular changes to DNA methylation and gene expression, and environmental factors, such as severe external challenges or adversities, can moderate these age-related changes. Yet, it remains unclear whether environmental adversities affect gene regulation via the same molecular pathways as chronological, or 'primary', aging. Investigating molecular aging in naturalistic animal populations can fill this gap by providing insight into shared molecular mechanisms of aging and the effects of a greater diversity of environmental adversities - particularly those that can be challenging to study in humans or laboratory organisms. Here, we characterised molecular aging - specifically, CpG methylation - in a sample of free-ranging rhesus macaques living off the coast of Puerto Rico (n samples = 571, n individuals = 499), which endured a major hurricane during our study. Age was associated with methylation at 78,661 sites (31% of all sites tested). Age-associated hypermethylation occurred more frequently in areas of active gene regulation, while hypomethylation was enriched in regions that show less activity in immune cells, suggesting these regions may become de-repressed in older individuals. Age-associated hypomethylation also co-occurred with increased chromatin accessibility while hypermethylation showed the opposite trend, hinting at a coordinated, multi-level loss of epigenetic stability during aging. We detected 32,048 CpG sites significantly associated with exposure to a hurricane, and these sites overlapped age-associated sites, most strongly in regulatory regions and most weakly in quiescent regions. Together, our results suggest that environmental adversity may contribute to aging-related molecular phenotypes in regions of active gene transcription, but that primary aging has specific signatures in non-regulatory regions.
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Exposure to adversity during early life is linked to lasting detrimental effects on evolutionary fitness across many taxa. However, due to the challenges of collecting longitudinal data, especially in species where one sex disperses, direct evidence from long-lived species remains relatively scarce. Here we test the effects of early life adversity on male and female longevity in a free-ranging population of rhesus macaques (Macaca mulatta) at Cayo Santiago, Puerto Rico. We leveraged six decades of data to quantify the relative importance of ten forms of early life adversity for 6,599 macaques (3,230 male, 3,369 female), with a smaller sample size (N=299) for one form of adversity (maternal social isolation) which required high-resolution behavioral data. We found that individuals who experienced more early life adversity died earlier than those who experienced less adversity. Mortality risk was highest during early life, defined as birth to four years old, suggesting acute survival effects of adversity, but heightened mortality risk was also present in macaques who survived to adulthood. Females and males were affected differently by some forms of adversity, and these differences might be driven by varying energetic demands, female philopatry, and male dispersal. By leveraging data on thousands of macaques collected over decades, our results show that the fitness consequences of early life adversity are not uniform across individuals but vary as a function of the type of adversity, timing, and social context, and thus contribute to our limited but growing understanding of the evolution of early life sensitivities in long-lived species.
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Photoreceptors in the retina are specialized neuronal cells that perceive light and play a central role in the visual system. Damage to photoreceptors is a clinical feature often associated with various retinal degenerative disorders. The photoreceptor bed comprises a unique extracellular matrix (ECM) scaffold often described as the interphotoreceptor matrix (IPM) in the subretinal space, vital during retinal development and homeostasis. In this study, we used focused ion beam scanning electron microscopy (FIB-SEM) and transmission electron microscopy (TEM) to analyze the ultrastructural architecture of the retinal pigmented epithelium (RPE)-photoreceptor complex in mice. Additionally, we describe methods for retinal preparation in EM imaging. TEM images display ultrastructural retina layers, including Bruch's membrane and the interdigitation zone (IZ). The 3-dimensional reconstruction of the outer retina revealed individual photoreceptors, the connection between their inner and outer segment via the photoreceptor cilia, and photoreceptor interaction with the RPE ciliary processes. Our findings highlight the importance of FIB-SEM in deciphering the ultrastructural details of RPE-photoreceptor interactions in the IPM complex which are essential for the maintenance of retinal architecture.
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Reproductive strategies are defined by expenditures of time and energy devoted to mating effort, which increases mating opportunities, and parenting effort, which enhances the survival of offspring. We examine tradeoffs between mating effort and parenting effort in male olive baboons, Papio anubis, a species in which males compete for mating opportunities, but also form ties to lactating females (primary associations) that represent a form of parenting effort. Males that are involved in more primary associations invest less in mating effort than males who are involved in fewer primary associations. Males that are involved in more primary associations play a smaller role in establishing proximity to their primary associates than other males, suggesting that males operate under temporal constraints. There is also some evidence that involvement in primary associations negatively affects paternity success. Taken together, the data suggest that males face tradeoffs between mating effort and parenting effort.
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Adverse experiences in early life are associated with aging-related disease risk and mortality across many species. In humans, confounding factors, as well as the difficulty of directly measuring experiences and outcomes from birth till death, make it challenging to identify how early life adversity impacts aging and health. These challenges can be mitigated, in part, through the study of non-human animals, which are exposed to parallel forms of adversity and can age similarly to humans. Furthermore, studying the links between early life adversity and aging in natural populations of non-human animals provides an excellent opportunity to better understand the social and ecological pressures that shaped the evolution of early life sensitivities. Here, we highlight ongoing and future research directions that we believe will most effectively contribute to our understanding of the evolution of early life sensitivities and their repercussions.
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Envejecimiento , Estrés Fisiológico , Animales , Modelos BiológicosRESUMEN
Social bonds enhance fitness in many group-living animals, generating interest in the processes that create individual variation in sociality. Previous work on female baboons shows that early life adversity and temperament both influence social connectedness in adulthood. Early life adversity might shape sociality by reducing ability to invest in social relationships or through effects on attractiveness as a social partner. We examine how females' early life adversity predicts sociality and temperament in wild olive baboons, and evaluate whether temperament mediates the relationship between early life adversity and sociality. We use behavioural data on 31 females to quantify sociality. We measure interaction style as the tendency to produce grunts (signals of benign intent) in contexts in which the vocalization does not produce immediate benefits to the actor. Early life adversity was negatively correlated with overall sociality, but was a stronger predictor of social behaviours received than behaviours initiated. Females who experienced less early life adversity had more benign interaction styles and benign interaction styles were associated with receiving more social behaviours. Interaction style may partially mediate the association between early life adversity and sociality. These analyses add to our growing understanding of the processes connecting early life experiences to adult sociality.
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Conducta Social , Estrés Psicológico , Animales , Femenino , Papio anubis , Comunicación AnimalRESUMEN
INTRODUCTION: Affordable virtual reality (VR) technology is now widely available. Billions of dollars are currently being invested into improving and mass producing VR and augmented reality products. PURPOSE OF THE STUDY: The purpose of the present study is to explore the potential of immersive VR to make physical therapy/occupational therapy less painful, more fun, and to help motivate patients to cooperate with their hand therapist. DISCUSSION: The following topics are covered: a) psychological influences on pain perception, b) the logic of how VR analgesia works, c) evidence for reduction of acute procedural pain during hand therapy, d) recent major advances in VR technology, and e) future directions-immersive VR embodiment therapy for phantom limb (chronic) pain. CONCLUSION: VR hand therapy has potential for a wide range of patient populations needing hand therapy, including acute pain and potentially chronic pain patients. Being in VR helps reduce the patients' pain, making it less painful for patients to move their hand/fingers during hand therapy, and gamified VR can help motivate the patient to perform therapeutic hand exercises, and make hand therapy more fun. In addition, VR camera-based hand tracking technology may be used to help therapists monitor how well patients are doing their hand therapy exercises, and to quantify whether adherence to treatment increases long-term functionality. Additional research and development into using VR as a tool for hand therapist is recommended for both acute pain and persistent pain patient populations.