Bats: Secrets of Extended Healthspan

Of all mammals, bat possess the most unique and peculiar adaptations that render them as excellent models to investigate the mechanisms of extended longevity and potentially halted senescence. Indeed, they are the longest-lived mammals relative to their body size, with the oldest bat caught being >41 years old, living approx. 8 times longer than expected. Bats defy the ‘rate-of-living’ theories that propose a positive correlation between body size and longevity as they use twice the energy as other species of considerable size, but live far longer. The mechanisms that bats use to avoid the negative physiological effects of their heightened metabolism and deal with an increased production of deleterious Reactive Oxygen Species (ROS) is not known, however it is suggested that they either prevent or repair ROS damage. Bats also appear to have resistance to many viral diseases such as rabies, SARS and Ebola and are the suspected reservoir species for a huge diversity of newly discovered viruses, including Sars-CoV-2 This suggests that their innate immunity is different to other mammals, perhaps playing a role in their unexpected longevity. Here the potential genomic basis for their rare immunity and exceptional longevity is explored across multiple bat genomes and divergent ageing and immune related markers (e.g. microbiome, telomeres, mitochondria, cellular dynamics, cytokine response) studied in wild bat populations. These findings provide a deeper understanding of the causal mechanisms of ageing and tolerant immunity, potentially uncovering the key molecular pathways that could be utilised to benefit society.

Presidential Symposium: Physiological vs. Molecular Clocks, Studies From Mice to Humans

Aging is associated with a functional decline in metabolic, physiological, proliferative, and tissue homeostasis leading to deterioration at the organismal level, and an increased risk for disease and death. Genetic, pharmacological and nutritional interventions have been successfully used to preserve metabolic health, which leads to preserved healthspan and extended longevity. However, the rate at which animals in a population become impaired by age-related frailty and disease is highly variable and several aging clocks that measure different age-modulated processes in the organism are being use as potential markers of the rate of aging. These molecular clocks allow to a more accurate quantification of the biological age of animals. Nevertheless, there is still room for further discussion in terms of the strengths and weaknesses of these biomarkers, in order to probe their biological significance, cellular mechanisms, and epidemiological potential to further explore their long-term benefit of increasing healthspan. This symposium will discuss new approaches to delineate physiological versus molecular clocks based on studies in mice and humans. We will also discuss species-specific metabolic mechanisms based on longitudinal studies in mice, monkeys and humans.

The lived experience of being a hundred years and over

<p>The twentieth century has seen a decline in mortality after the age of eighty and an increase in survival rates of the oldest of the old. Centenarians (people over a hundred years of age) are the fastest growing group of this population in developed countries; however qualitative research on the oldest of the old is limited. The primary aim of this study was to gain an understanding of the essence of lived experiences and meanings of extended longevity as perceived by centenarians. It also aimed to explore the role of lifestyle characteristics, family, social, health and cultural factors in regards to their prolonged existence. The research was conducted with ten centenarians aged between 100 and 106 years living in the Lower North Island namely Wairarapa, Kapiti and Wellington of Aotearoa New Zealand. Biographical Narrative Interpretive Method of inquiry was used to guide the data collection through face-to-face interviews using unstructured open ended questions. Colazzi’s phenomenological framework was employed for data analysis. There were common patterns throughout the life stories related by the centenarians and resilience and acceptance of life was notable. The centenarians spoke nonchalantly about their experience of turning a hundred, describing their birthday as; “Just another day.” Positive personalities and resilient nature were prominent features of the participants who all expressed a sense of acceptance and satisfaction with life and contentment with living in the present. All centenarians had a privileged upbringing and were nurtured during their childhood by their parents, grandparents and siblings and these interrelationships were ongoing at an intergenerational level. They had all kept themselves active as much as they could throughout their lifetime. The results suggest that nurturing has an important role in the survival of the oldest of old.</p>

The lived experience of being a hundred years and over

<p>The twentieth century has seen a decline in mortality after the age of eighty and an increase in survival rates of the oldest of the old. Centenarians (people over a hundred years of age) are the fastest growing group of this population in developed countries; however qualitative research on the oldest of the old is limited. The primary aim of this study was to gain an understanding of the essence of lived experiences and meanings of extended longevity as perceived by centenarians. It also aimed to explore the role of lifestyle characteristics, family, social, health and cultural factors in regards to their prolonged existence. The research was conducted with ten centenarians aged between 100 and 106 years living in the Lower North Island namely Wairarapa, Kapiti and Wellington of Aotearoa New Zealand. Biographical Narrative Interpretive Method of inquiry was used to guide the data collection through face-to-face interviews using unstructured open ended questions. Colazzi’s phenomenological framework was employed for data analysis. There were common patterns throughout the life stories related by the centenarians and resilience and acceptance of life was notable. The centenarians spoke nonchalantly about their experience of turning a hundred, describing their birthday as; “Just another day.” Positive personalities and resilient nature were prominent features of the participants who all expressed a sense of acceptance and satisfaction with life and contentment with living in the present. All centenarians had a privileged upbringing and were nurtured during their childhood by their parents, grandparents and siblings and these interrelationships were ongoing at an intergenerational level. They had all kept themselves active as much as they could throughout their lifetime. The results suggest that nurturing has an important role in the survival of the oldest of old.</p>

Reproductive Potential Impacts Body Maintenance Parameters and Global DNA Methylation in Honeybee Workers (Apis mellifera L.)

The widely accepted hypothesis in life history evolution about the trade-off between fecundity and longevity is not confirmed by long-living and highly fecund queens in eusocial insects. The fact that the queens and facultatively sterile workers usually arise from genetically identical eggs but differ in DNA methylation makes them a good model for studies on senescence, eusocial evolution, and epigenetics. Therefore, honeybees seem to be especially useful here because of long living rebel-workers (RW) with high reproductive potential recently described. Longevity, ovariole number, nosema tolerance, and global DNA methylation have been assayed in normal workers (NW) versus RW in hives and cages. RW always lived longer than NW and unexpectedly extended longevity of NW when they were together, similarly as the presence of a queen did. RW lived longer despite the fact that they had higher Nosema spore load; surprisingly they became infected more easily but tolerated the infection better. Global DNA methylation increased with age, being lower in RW than in NW. Therefore, RW are queen-like considering global DNA methylation and the link between fecundity, longevity, and body maintenance. Presented features of RW expands possibilities of the use of honeybees as a model for studies on senescence, nosemosis, eusocial evolution, and epigenetics.

Intergenerational hormesis is regulated by heritable 18S rRNA methylation

SummaryHeritable non-genetic information can regulate a variety of complex phenotypes. However, what specific non-genetic cues are transmitted from parents to their descendants are poorly understood. Here, we perform metabolic methyl-labelling experiments to track the heritable transmission of methylation from ancestors to their descendants in the nematode Caenorhabditis elegans. We find that methylation is transmitted to descendants in proteins, RNA, DNA and lipids. We further find that in response to parental starvation, fed naïve progeny display reduced fertility, increased heat stress resistance, and extended longevity. This intergenerational hormesis is accompanied by a heritable increase in N6’-dimethyl adenosine (m6,2A) on the 18S ribosomal RNA at adenosines 1735 and 1736. We identified the conserved DIMT-1 as the m6,2A methyltransferase in C. elegans and find that dimt-1 is required for the intergenerational hormesis phenotypes. This study provides the first labeling and tracking of heritable non-genetic material across generations and demonstrates the importance of rRNA methylation for regulating the heritable response to starvation.

Aging: What We Can Learn From Elephants

Elephants are large-brained, social mammals with a long lifespan. Studies of elephants can provide insight into the aging process, which may be relevant to understanding diseases that affect elderly humans because of their shared characteristics that have arisen through independent evolution. Elephants become sexually mature at 12 to 14 years of age and are known to live into, and past, their 7th decade of life. Because of their relatively long lifespans, elephants may have evolved mechanisms to counter age-associated morbidities, such as cancer and cognitive decline. Elephants rely heavily on their memory, and engage in multiple levels of competitive and collaborative relationships because they live in a fission-fusion system. Female matrilineal relatives and dependent offspring form tight family units led by an older-aged matriarch, who serves as the primary repository for social and ecological knowledge in the herd. Similar to humans, elephants demonstrate a dependence on social bonds, memory, and cognition to navigate their environment, behaviors that might be associated with specializations of brain anatomy. Compared with other mammals, the elephant hippocampus is proportionally smaller, whereas the temporal lobe is disproportionately large and expands laterally. The elephant cerebellum is also relatively enlarged, and the cerebral cortex is highly convoluted with numerous gyral folds, more than in humans. Last, an interesting characteristic unique to elephants is the presence of at least 20 copies of the TP53 tumor suppressor gene. Humans have only a single copy. TP53 encodes for the p53 protein, which is known to orchestrate cellular response to DNA damage. The effects of these multiple copies of TP53 are still being investigated, but it may be to protect elephants against multiple age-related diseases. For these reasons, among others, studies of elephants would be highly informative for aging research. Elephants present an underappreciated opportunity to explore further common principles of aging in a large-brained mammal with extended longevity. Such research can contribute to contextualizing our knowledge of age-associated morbidities in humans.

Diet and Leukocyte Telomere Length in a Population with Extended Longevity: The Costa Rican Longevity and Healthy Aging Study (CRELES)

Elderly Costa Ricans have lower mortality rates compared to their counterparts from developed countries. Reasons for this survival advantage are not completely known. In the present study, we aimed to identify dietary factors associated with leukocyte telomere length (LTL), a marker of biologic aging, in the elderly population of Costa Rica. We conducted prospective analysis in 909 participants aged 60+ years from the Costa Rican Longevity and Healthy Aging Study (CRELES). We used a food frequency questionnaire to assess usual diet. We calculated dietary patterns using Principal Component Analysis (PCA). We used generalized linear models to examine the association of dietary patterns and food groups with leukocyte telomere length. We found two major dietary patterns explaining 9.15% and 7.18% of the total variation of food intake, respectively. The first dietary pattern, which represents a traditional Costa Rican rice and beans pattern, was more frequent in rural parts of the country and was positively associated with baseline LTL: β (95% CI) = 42.0 base-pairs (bp) (9.9 bp, 74.1 bp) per one-unit increase of the traditional dietary pattern. In analysis of individual food groups, intake of grains was positively associated with baseline LTL: β (95% CI) = 43.6 bp (13.9 bp, 73.3 bp) per one-serving/day increase of consumption of grains. Our results suggest that dietary factors, in particular a traditional food pattern, are associated with telomere length and may contribute to the extended longevity of elderly Costa Ricans.

The Impact of the Coronavirus (Sars-Cov-2) Lockdown on Crime in New York and London, March-June 2020: A Comparative Study

The objective of this paper is to assess the relationship between The Spring 2020 COVID-19 Lockdown and the levels of crime in New York City (NYC) and London. Our proposition, derived from the Routine Activity Theory (RAT), the ‘breaches’ theory and input from the 2020 research on lockdown and crime, hypothesised that lockdown measures would lead to reductions in crime. The crime categories selected for this study were: homicide, rape, robbery, violence against a person, burglary, theft and vehicle theft. T-test, F-test and the Ordinary Least Squares (OLS) regression calculations were used to test the hypotheses. The four-month lockdown period in 2020 produced a 15% and 31% crime reduction in NYC and London, respectively. In the case of London, the overall results indicate that changes in routine human activities were indeed largely correlated with the reduction in crime. However, crime patterns in NYC in spring 2020 turned out to be inconsistent. A comparison of crime patterns under lockdown proved dissimilarity between NYC and London. The two-city comparison indicates that crime change related to lockdown may vary across crime types, places, and timespans or may have a detrimental effect on crime levels. The study may be considered suitable for replication and elaboration, particularly in view of the extended longevity of lockdown measures.