The Danaid Theory of Aging

The classical evolutionary theories of aging suggest that aging evolves due to insufficient selective pressure against it. In these theories, declining selection pressure with age leads to aging through genes or resource allocations, implying that aging could potentially be stalled were genes, resource allocation, or selection pressure somewhat different. While these classical evolutionary theories are undeniably part of a description of the evolution of aging, they do not explain the diversity of aging patterns, and they do not constitute the only possible evolutionary explanation. Without denying selection pressure a role in the evolution of aging, we argue that the origin and diversity of aging should also be sought in the nature and evolution of organisms that are, from their very physiological make up, unmaintainable. Drawing on advances in developmental biology, genetics, biochemistry, and complex systems theory since the classical theories emerged, we propose a fresh evolutionary-mechanistic theory of aging, the Danaid theory. We argue that, in complex forms of life like humans, various restrictions on maintenance and repair may be inherent, and we show how such restrictions are laid out during development. We further argue that there is systematic variation in these constraints across taxa, and that this is a crucial factor determining variation in aging and lifespan across the tree of life. Accordingly, the core challenge for the field going forward is to map and understand the mosaic of constraints, trade-offs, chance events, and selective pressures that shape aging in diverse ways across diverse taxa.

Lifespan Extension in Long-Lived Vertebrates Rooted in Ecological Adaptation

Contemporary studies on aging and longevity have largely overlooked the role that adaptation plays in lifespan variation across species. Emerging evidence indicates that the genetic signals of extended lifespan may be maintained by natural selection, suggesting that longevity could be a product of organismal adaptation. The mechanisms of adaptation in long-lived animals are believed to account for the modification of physiological function. Here, we first review recent progress in comparative biology of long-lived animals, together with the emergence of adaptive genetic factors that control longevity and disease resistance. We then propose that hitchhiking of adaptive genetic changes is the basis for lifespan changes and suggest ways to test this evolutionary model. As individual adaptive or adaptation-linked mutations/substitutions generate specific forms of longevity effects, the cumulative beneficial effect is largely nonrandom and is indirectly favored by natural selection. We consider this concept in light of other proposed theories of aging and integrate these disparate ideas into an adaptive evolutionary model, highlighting strategies in decoding genetic factors of lifespan control.

Senescence in Bacteria and Its Underlying Mechanisms

Bacteria have been thought to flee senescence by dividing into two identical daughter cells, but this notion of immortality has changed over the last two decades. Asymmetry between the resulting daughter cells after binary fission is revealed in physiological function, cell growth, and survival probabilities and is expected from theoretical understanding. Since the discovery of senescence in morphologically identical but physiologically asymmetric dividing bacteria, the mechanisms of bacteria aging have been explored across levels of biological organization. Quantitative investigations are heavily biased toward Escherichia coli and on the role of inclusion bodies—clusters of misfolded proteins. Despite intensive efforts to date, it is not evident if and how inclusion bodies, a phenotype linked to the loss of proteostasis and one of the consequences of a chain of reactions triggered by reactive oxygen species, contribute to senescence in bacteria. Recent findings in bacteria question that inclusion bodies are only deleterious, illustrated by fitness advantages of cells holding inclusion bodies under varying environmental conditions. The contributions of other hallmarks of aging, identified for metazoans, remain elusive. For instance, genomic instability appears to be age independent, epigenetic alterations might be little age specific, and other hallmarks do not play a major role in bacteria systems. What is surprising is that, on the one hand, classical senescence patterns, such as an early exponential increase in mortality followed by late age mortality plateaus, are found, but, on the other hand, identifying mechanisms that link to these patterns is challenging. Senescence patterns are sensitive to environmental conditions and to genetic background, even within species, which suggests diverse evolutionary selective forces on senescence that go beyond generalized expectations of classical evolutionary theories of aging. Given the molecular tool kits available in bacteria, the high control of experimental conditions, the high-throughput data collection using microfluidic systems, and the ease of life cell imaging of fluorescently marked transcription, translation, and proteomic dynamics, in combination with the simple demographics of growth, division, and mortality of bacteria, make the challenges surprising. The diversity of mechanisms and patterns revealed and their environmental dependencies not only present challenges but also open exciting opportunities for the discovery and deeper understanding of aging and its mechanisms, maybe beyond bacteria and aging.

Circulatory systems and mortality rates

Aging is a complex process involving multiple factors and subcellular processes, ultimately leading to the death of an organism. The microscopic processes that cause aging are relatively well understood and effective macroscopic theories help explain the universality of aging in complex systems. However, these theories fail to explain the diversity of aging observed for various lifeforms. As such, more complete "mesoscopic" theories of aging are needed, combining the biophysical details of microscopic failure and the macroscopic structure of complex systems. Here we explore two models: (1) a network theoretic model, and (2) a convection diffusion model emphasizing the biophysical details of communicated signals. The first model allows us to explore the effects of connectivity structures on aging. In our second model, cells interact through cooperative and antagonistic factors. We find by varying the ratio at which these factors affect cell death, as well as the reaction kinetics, diffusive and flow parameters, we obtain a wide diversity of mortality curves. As such, the connectivity structures as well as the biophysical details of how various factors are transported in an organism may explain the diversity of aging observed across different lifeforms.

Sex differences in biological aging with a focus on human studies

Aging is a complex biological process characterized by hallmark features accumulating over the life course, shaping the individual's aging trajectory and subsequent disease risks. There is substantial individual variability in the aging process between men and women. In general, women live longer than men, consistent with lower biological ages as assessed by molecular biomarkers, but there is a paradox. Women are frailer and have worse health at the end of life, while men still perform better in physical function examinations. Moreover, many age-related diseases show sex-specific patterns. In this review, we aim to summarize the current knowledge on sexual dimorphism in human studies, with support from animal research, on biological aging and illnesses. We also attempt to place it in the context of the theories of aging, as well as discuss the explanations for the sex differences, for example, the sex-chromosome linked mechanisms and hormonally driven differences.

Gerotranscendence and Alaska Native Successful Aging in the Aleutian Pribilof Islands, Alaska

The population of the United States is aging and by 2045 it is projected that approximately 1 in every 6 Alaskans will be 65+. Delivering healthcare and meeting the needs of older Alaskans in their community is critical to supporting healthy aging and community sustainability. Alaska Native (AN) Elders are underserved with very few studies providing an emic perspective on their experience aging. This research opens the door and allows us a glimpse of the AN Elder experience of aging: the values, beliefs, and behaviors that allow them to age well. This study highlights the characteristics and activities of AN Elders in the Aleutian and Pribilof Islands to further develop the model of AN successful aging. There are many theories of aging and this study explores a cross-cultural understanding of gerotranscendence - the personal and interpersonal changes that result from successful aging or achieving Eldership. This study interviewed Elders in two communities of the Aleutian and Pribilof Islands region. Using 22 standardized questions based on the explanatory model, researchers facilitated discussion of what it means to be an Elder and age successfully. Employing thematic analysis, interview transcripts were analyzed for themes to organize the data. Themes were organized into 5 core elements of successful aging with specific emphasis on values, beliefs, and behaviors that were protective and helped them adapt to aging-related changes. Interview content, meaning, and themes support the four elements of the AN model of successful aging developed by Lewis (The Gerontologist, 51(4), 540-549, 2011): Mental and Emotional Wellbeing, Spirituality, Purposefulness and Engagement, and Physical Health. Elders’ stories highlight the importance of reflection, personal growth, and psychosocial development. Elders who more strongly identified with their role in the community described how their perspective had changed and they shared stories that emphasized culture, connection to the land, and enjoyment of daily activities that resulted in increased life satisfaction. Elders provided clear evidence that they experienced aspects of gerotranscendence, which Tornstam (Journal of Aging Studies, 11(2), 143-154, 1997) categorized as the cosmic dimension, the self, and social and personal relationships. Elders adapting to aging-related changes and embracing their role as an Elder provided the greatest evidence of gerotranscendence - they developed new perspectives on life, took on new roles within the community, and experienced a shift in mindset that reinforced the importance of culture, tradition, and the Native Way of Life. This research allowed AN Elders to share their experiences, define successful aging, and expand the concept of Eldership to include changes in mindset, values, and relationships with themselves and others. The study is a framework to help us better understand the experiences of AN Elders aging successfully and the wisdom they wish to impart to others to help them learn to live healthy and meaningful lives.