An exploration of longevity research, delving into the science behind living longer. As humankind strives to transcend the limits of the lifespan, scientists are hard at work investigating why some people live longer than others. Despite the wide variation in the human lifespan, the underlying factor of life is our cells. Uncovering the scientific basis of life is tantamount to transcending its limits. Over almost a century, an extraordinary understanding of cells has been achieved, from which new strategies have emerged to prevent their deterioration and promote repair after damage. This, in turn, provides the means to ensuring that life lives longer, not only cells but ultimately organisms as well.
1. Introduction to Longevity Research
No matter how long the evolutionary tale, the scientific basis of life asks some of the most basic questions: What is life? How did it originate? How does it work? Where is it going? More than a century ago, life was chosen as an ideal subject for scientists. Nevertheless, after more than a century, the account is more a reconstruction of life’s physical features rather than an understanding of how it works. Comprehending the living cell requires an understanding of the chemicals and processes within it. To a large extent, biological processes can be viewed as driven by the flow and recycling of energy, the flow of matter, and the cycle of information. Of course, much of this has been understood in great chemical detail. Yet, how complex cells built upon notes in physicochemical reconstruction’s survive the vicissitudes of the natural world remains a conceptual conundrum even when their rational basis is grasped [1].
1.1. Defining Longevity and Its Importance
Longevity is defined here as an extended lifespan that is free of age-related decrements in multiple systems. Curiously, there exist individuals at the extremes of the lifespan distribution that reveal some secrets of longevity. Some of these individuals originate from longevity-enriched families, which have a propensity to be long-lived and evade age-related morbidity [2]. Human longevity has been the target of genealogical studies for over a century, and several types of studies have evidenced that parental longevity could be considered a proxy for lifespan. Members of long-lived families show a compression of late life morbidity (extended healthspan), and although these results are not universally accepted, investigating the genetics of these individuals might help identify novel mechanisms involved in healthy aging that can be targeted by therapeutic interventions.
The goal of longevity research is not simply to find drugs that will increase maximum life span (in non-phtv mutant worms, this is 26 days). A longer maximum life span will not guarantee a better quality of life, and it may not even be achievable with best efforts [1]. This is similar to the futility of seeking drugs that will “optimize” organismal form and size, or “improve” the quality of ecological communities. Accordingly, designing, developing, and using drugs to promote longevity will require an understanding of healthy longevity in the fullest sense.
2. Genetics and Longevity
Human beings cannot choose their birth dates, but they can adopt various lifestyles, assistive medical devices, medicines, etc. [3] that can considerably influence their life spans. The result is an increasing interest among scientists and non-scientists alike in the biology of longevity, as witnessed by the growth of the Internet sites with their own reviews, publications, and books. The remarks that follow focus on how the genetic endowment and its evolution can influence longevity. Longevity depends on the type of species, diet or food, and external environment. Just to give an example (found in the literature), among animals, the following characteristics are associated with greater longevity: heavy weight, being herbivorous rather than carnivorous, and being monogamous rather than polygamous.
An interesting reflection stems from a variety of animals. The naked mole rat (Heterocephalus glaber) is a long-lived rodent (up to 30 years) and being almost devoid of cancer. This species has an abnormal architecture of the genome: more highly GC-rich chromosome regions, overall hypermethylation, and retention of non-coding RNA transcripts accounting for 54% of the genome. Fish, corvids, and parrots are particularly long-lived birds. Fishes are known for their great longevity diversity (for example, the soft-shell clam (Mya arenaria) is around 300 years). Both fishes and birds possess high metabolic rates, paralleled with their short life spans, but also great longevity diversity. The additional factor that can influence longevity is the environmental adaptability of a species.
2.1. Role of Genetics in Determining Lifespan
Human lifespan is highly variable, with a range of 0–122 years. The disparity in lifespan is often greater when various groups are compared, such as African and Asian countries, or high- and low-income regions. However, within apparently genetically uniform populations, like Icelandic and Ashkenazi Jew populations, the range is still considerable, highlighting the complexity in understanding the factors influencing human lifespan [3]. Among the determinants of lifespan, genetic factors may play a crucial role. The general comparative biology of lifespan suggests that species share a common genetic basis that can influence survival following reproduction. However, the genome-wide resources for studying this topic in humans are limited. Older organisms exhibit a greater variability in life history traits, and the greater this variability, the less stable these traits. The dispersal of individuals from a population depends on their initial life history traits. Lifespan evolvement is determined by the interplay of ecology, life history traits, and genetic components. Since such data is not available for humans, results regarding genes affecting lifespan are less conclusive than for other model organisms. Nevertheless, various studies shed light on the genetic determinants of human lifespan. The importance of genetic factors is evident in families clustered for longevity since a heritable factor must underlie such clustering. This has been verified in sibling and spouse studies of centenarians. Using the age of death of monozygotic and dizygotic twins, a genetic component of lifespan in humans was first estimated 30 years ago. More recent estimates suggest that about 25% of the variation in human longevity can be due to genetic factors [4]. In centenarians, the genetic contribution reaches about 33% for women and 48% for men. However, the genetic contribution to survival initially is small (about 7% for survival up to 60 years of age) and increases with age. The heritability of longevity varies between populations, and there is a dynamic interplay between genetic and environmental variation in health and longevity. Overall, the genetics of longevity are closely associated with protection against age-related diseases, especially atherosclerotic cardio- and cerebrovascular diseases.
3. Lifestyle Factors and Longevity
Recent research has shown that an increasing proportion of the population in the developed countries lives to very advanced age. Although current knowledge of the determinants of longevity is limited, it is known that longevity is influenced by biological, environmental, and psychosocial factors [5]. Since environmental and psychosocial factors are considered modifiable risk factors, they are of great interest; and knowledge of these factors is especially relevant because they are amenable to intervention. The associations of lifestyle factors with mortality in a very old population have, however, been rarely studied. Data from the Swedish Longitudinal Studies of Aging (SLSA) were used to examine the associations of independent and combinations of various modifiable factors with median age at death in a cohort aged 75 or more years.
A healthier lifestyle, its specific components, and some combinations of the specific factors have been associated with subsequent survival. However, the associations with overall survival of some other factors, particularly social network, have been weak and inconsistent, mainly because previous studies have addressed these factors individually rather than in combination. Furthermore, the possible existence of a threshold level for certain factors, such as physical activity, diet, and alcohol intake, has rarely been studied, and evidence suggests that some associations vary with use of medication and health status among the elderly individuals regarded as being frail by health status. In addition to factors that impact longevity, it would also be important to consider how these factors interact with one another, as they may act synergistically and thus have an even larger effect on overall lifespan.
3.1. Diet and Nutrition
As more people live longer, it is important to consider ways to promote healthy aging and longevity. Research into the causes of longer life has identified several common factors that exist in areas characterized by a high rate of centenarians. A regular social life, stress reduction, moderate drink and food intake, active living and regular exercise as well as a healthy diet, which is part of the traditional Mediterranean lifestyle, seem to be relevant for healthy longevity [6].
The Mediterranean diet has stood out in recent years as a successful alternative to current dietary patterns that has contributed to a lowered risk of obesity and its consequences. Further investigation of the diet reveals characteristics that promote longevity and avoid age-associated diseases. Dietary habits in the Mediterranean diet include lower total fat and red meat intake, use of healthy oils such as olive oil, increased consumption of fruits and vegetables, fish and poultry instead of red meats as well as nuts and legumes [7]. In addition to these nutritional aspects, many factors such as drinking habits, lifestyle, education status and socio-economic level are also suggested to influence beneficial health effects of the diet.
4. Exercise and Longevity
The relationships between physical activity, function, and longevity were examined in a sample of 169 older men aged 81-89, followed for 7 years. The highest category of physical activity was associated with less decline in physical function and longevity. A strong association between resting heart rate and longevity was also found. Men aged 81-89 had a resting heart rate of 66 beats per minute, while the average resting heart rate was 72 for older men who died [7]. The relationships between self-reported loneliness, health, and longevity among the elderly were examined. A random sample of 1818 elderly people was employed in a longitudinal study of 4 years. There was found a reciprocal relationship between health and loneliness in old age. The sense of being lonely increased the risk of poor health in later years. The sense of poor health increased the risk of suffering from loneliness. The term “social support” is suggested to be more appropriate than “loneliness” to describe the social context of health and longevity.
The majority of societies have emerged in the Mediterranean area. Their evolution was highly influenced by environmental factors. Several significant elements, which determine the evolution of Mediterranean societies, are presented. They represent the environment as a unique scenario for both good quality of life and longevity. It is proposed to consider Mediterranean recovery with the concomitance of maintaining longevity societies and converging some aspects of continental ups and downs. The surprising number of persons who live to a 100 years and longer has prompted interest in their general lifestyles. Awareness of factors associated with their longevity may lead to ways of avoiding some health hazards, thereby promoting a longer life. There will be presented findings bearing on physical activity, diet, and psychosocial influences on longevity. In addition, some representative examples of the 100 years plus cohort will be chronicled to highlight uniqueness in lifestyles.
4.1. Types of Exercise for Longevity
The discussion now moves on to consider the different types of exercise and their effects on lifespan and the years lived in good health. A high participation in different types of physical activity will ensure a greater longevity and disability-free life expectancy, but some activities seem to contribute even more than others. It is outside the scope of this discussion to summarize the scientific literature on the topic, since there are excellent reviews available. One recent paper presented several types of exercise that appear interesting in this aspect. Information is provided here on what these types of exercise are, and readers interested in doing their best would be wise to incorporate them into their daily routines.
Physical activity has a huge positive impact on health, lifespan and wellness, and studies suggest a target of five hours of moderate physical activity a week for having an excellent health and a long life expectancy. An exciting field within biology and medicine is presently about the understanding of the cellular and molecular basis for aging, and many practical implications from this knowledge are presently beginning to be put forward [8]. It has however been noted that extending lifespan might come at a cost of reduced health. Here, it is argued that exercise used to ameliorate health and prolong lifespan can actually extend both things very efficiently.
5. Mental Health and Longevity
While decades of research focus on the role that genes, behavior, and environment play in lifespan, mental health also plays a critical role that is largely unexamined. A growing body of evidence suggests that those who remain mentally sharp, engaged, and finish life with no known signs of neurodegenerative disease and who report a high level of mental health and well-being also live longer. They alluded to an abundance of national longitudinal studies, and recent investigations of the links between mental health and longevity in very large cohorts and healthcare databases using data from hospital records, survey data, and Social Security Administration records while controlling for sex, race, education, income, and other sociodemographic factors that predict health and longevity.
Subjective well-being was originally high at the beginning of adult life, then seemed to decline progressively until it hit the rock bottom in middle age, producing the so-called mid-life crisis, but then appeared to start rising again. A common finding across investigations is that of better mental health and increased satisfaction with life during the second half of adult life. Older age is reportedly associated with a gradual change in attitude, such as greater acceptance of physical limitations, contentedness with past accomplishments, and a more realistic appraisal of strengths and limitations [9]. Older adults perceived their stressors as less severe. Emotional satisfaction takes precedence over information pursuit in later life. Despite aging-associated loss of fertility and decline in physical health, subjective well-being and happiness increase after middle age.
There are reasons to believe that depression and its neurobiological consequences hasten clinical onset and accelerate the course of age-related diseases and conditions, including Alzheimer’s disease, Parkinson’s disease, stroke, and cardiovascular disease, and also hasten death from these conditions. Understanding the links between longevity and mental health is imperative for developing therapeutic and public health initiatives to promote health and longevity and to narrow the gap in well-being and longevity between the older and younger generations [10].
5.1. Cognitive Activities and Longevity
Many questions about cognitive activities and longevity have not been sufficiently addressed, such as the types of cognitive activities that impact longevity, the degree of cognitive activities, the emphasis on stimulating cognitive activities, and conditional relationship with other factors. Seeking solutions to these questions can improve the understanding of the factors that impact longevity. To investigate the relationship between cognitive activities and longevity, the Chinese Longitudinal Healthy Longevity Survey, covering the whole day and a wide range of cognitive activities, was used. The 10 cognitive activities with better longevity-related commonality were explored using the Four-Group Method, and the degree of cognitive activities was defined. By conducting a series of control analyses, conditioning variable interactions, and robustness tests, strong evidence was found supporting the following assumptions regarding cognitive activities and longevity.
Longevity-related cognitive activities widely occur across a variety of smart devices and traditional cognitive methods, such as reading; chatting; using the internet; playing cards, chess, and logographic games; and writing. Longevity is associated with such cognitive activities regardless of social status, education, and lifestyle. This association is stronger for those who engage in more cognitive activities and stimulating cognitive activities with good interactions and greater effects of stimulating cognitive activities growing with cognitive activity degree. Outside of cognitive activities, variables impacting longevity include gender, better health status, and smoking. Longevity does not rely on a specific demographic, but it is sensitive to cognitive activity occurrence patterns, with good adaptability [11]. There are no known retention mechanisms or methods for habitual cognitive activities that impact longevity to identify the subjects.
6. Environmental Factors and Longevity
The focus of research is typically on understanding biological pathways that may lead to increased health span and as a result increased longevity. Many studies of model organisms are correlational; observational data suggest that interactions with the environment may significantly influence overall lifespan. A primordial environmental influence on longevity is selection; it has been noted that there are regional and ethnic differences in the distribution of long-lived individuals. Recently, twenty novel genomic loci were identified which affect longevity in the Ashkenazi Jewish population and are associated with latitude [4]. Thus, environmental influences on longevity are more complex than temperature or humidity; disparities in diet, lifestyle, socioeconomic status, and pollution are all environmental effects that have been suggested to influence longevity and that can co-vary with geography. Human amniotic epithelial cells (hAECs), a population of somatic stem cells derived from the amniotic fluid and membrane, display many features of pluripotent stem cells, including unlimited self-renewal, differentiation into any somatic cell type, and a genomic profile resembling human embryonic stem cells (hESCs). When evaluated in a preclinical model of acute radiation toxicity, hAECs were found to be effective when administered up to 72 hours after injury. Essentially all treatment groups uniformly survived severe exposure the longer administration windows. When tested on the late reacting array including lung, gut, liver, and bone marrow, treated animals were protected and recovered from radiation-induced changes better than untreated use [7].
6.1. Impact of Pollution on Longevity
Narrowing down the discussion on environmental factors, pollution is the specific topic here. The inquiry is intended to elucidate how pollution can adversely affect human longevity. Starting from a broader perspective of environmental coverage, pollution contrasts with other factors like trees and green parks. References from various scientific publications question the potential ramifications of environmental pollution on the longevity of human lifespan [12]. A quantum of effect on the human lifespan covering this portion of longevity research is again emphasized herein. As pollution has become the most acute problem for all living beings on earth, it is a requirement of this research to specifically address its negative influence on longevity.
In the era of numerous harmful pollutants like the increasing amount of CO2 and other trapped poisonous gases in the atmosphere, aquatic sources with heavy metals in running water, plastic choking everywhere, industrial and chemical wastes in provision plants, and so on, it has been estimated that up to 40% of premature mortality is related to the adverse effects of pollution [13]. The newly published paper from Nature demonstrated 3–4 years of the decrease in longevity among the weathered qualifiers or huge population from safe lifelong exposures regarding the population burden by events like the Bhopal gas tragedy or Chernobyl nuclear disaster, despite its having completely different chemical identities. There is another WHO report published in 2017 stating that a huge number of years of life have been lost (YLL) globally due to pollution.
7. Technological Advances in Longevity Research
Biotechnology is the one field that has advanced as the Human Genome Project has refined the reference sequence or blueprint of life. The I-DOT life science bill proposal will fund several projects that will lay the foundation for a “Frankenstein” biotechnology. Countries like China and Russia have already initiated these target projects. The resulting massive technological capabilities will have unprecedented military applications that will destabilize the global balance of power and provoke hostile actions [14]. Modern fights against aging are based on experimental resilience studies of animal species with exceptional longevities. This field is still in its infancy, though remarkable successes have been achieved.
A study attempts to provide a comprehensive overview of this burgeoning discipline, the status of the main knowledge gaps, and the recent technological advances expected to fill them [15]. Longevity research is the study of the determination, causes, and mechanisms of lifespan and longevity difference in similar species. This understanding is expected to guide the development of biotechnology targeting enhanced health and longevity of human beings, especially during flourishing old ages.
7.1. Biotechnology and Longevity
The scientific advances in the last half a century in biotechnology and engineering, artificial intelligence and long-range technologies have taken great strides towards understanding humans’ biggest fear: death. Death has driven humanity to positive achievements—advancing arts, sports, architecture, science, chemistry, education, engineering, etc. Scientists around the globe are working day and night to replace the default fate of humans and other biological creatures, death. Angles, time machines and other magical concepts have appeared in the imagination of poets, nevertheless, the deepest desire of mankind is to live healthy and forever [14].
Biotechnology and engineering advancements give the hope of getting its implementation one day. The discoveries of large-scale single-cell omics and other technologies make a detailed understanding of aging processes feasible. Although this is in the cradle, it is a field to watch [15]. Biologist L. M. T. Leal work initiated an innovative direction. The rapidly increasing depth of understanding of aging processes, however, needs computer literacy in biomedicine. It is convincing though that such knowledge will be translated into detecting, monitoring, and repairing biological damage to aging.
8. Current Trends and Future Directions in Longevity Research
There are many exciting trends in longevity research today, with new discoveries about the aging process happening on a regular basis. Here are a few of them: Mast cells, a key part of the immune system, control the accumulation of senescent cells and are potential targets for new therapies [2]. The circadian clock plays an important role in the aging process and is being studied in longevity research for its potential to improve health. Microbiome composition can affect health and longevity, and therapies targeting the gut microbiome are being developed. Advances in synthetic biology and bioengineering have enabled the development of promising new longevity therapies. Multigenerational studies are providing new insights into human longevity.
There are many potential directions for future research in longevity science. Key unsolved scientific questions include: What is the nature of biological aging? Is aging a homeostatic process that can be calculated and controlled? Is it really possible to rejuvenate old tissues? There are also many possible new technologies that could be developed in the future, such as the ability to reprogram cells to turn them into whatever type of cell is needed. There may be cures or treatments for all cancers and heart disease, instant organ regeneration, and therapies to keep old biological tissues in youthful states. Other possible games changing technologies include: peptide replacement therapy to prevent, slow, and even reverse biological aging. Gene therapies to prevent diseases of aging or delay the aging process. Therapies to rejuvenate or replace immune system tissues. Repeating DNA sequence repairs (to prevent infections and aging). New nanotechnology and biotechnology to slow or stop cancer and neurodegeneration. Hypoxia-inducible factor inhibitors to prevent age-related vascular diseases.
8.1. Emerging Areas of Study
Aging research has entered a very exciting period where traditional scientific approaches are converging with clinical research and epidemiology. Technological advances such as next-generation sequencing technologies, genome-wide association studies, and the establishment of biobanks and consortia with large longitudinal datasets have brought aging research to a place that could not have been imagined back in the establishment of the National Institute on Aging. Aging and age-related disease are considered problems of systemic biology, and there is a concerted effort to adopt these approaches in aging research [16].
With remarkable advances in research over the last two decades, there have been significant discoveries of genes and biomarkers associated with healthy aging and exceptional aging. Successful studies in laboratory animals have laid out factors that have established roles in regulation of longevity. Questions that a decade ago were fundamental and often not even addressable such as exact molecular basis for the role of energy metabolism in aging are being investigated. Another important avenue of investigation with translational potential is the role of lipid metabolism in aging and disease vulnerability. In the human studies and in many species including simple model organisms such as Caenorhabditis elegans and Drosophila, lipid transport and lipid handling are common themes in human and laboratory aging studies. Taking a broader view, it will be necessary to distinguish between events that are coincident with aging and those that are driving aging [17].
9. Ethical Considerations in Longevity Research
When first proposing radical life extension, it is naïve to think politicians will consider the potential benefits and drawbacks and implement sensible policies. Instead, it would be prudent to anticipate and actively work to minimize worst-case scenarios when extreme healthspan or lifespan extension technologies first reach mass-market availability. Then, plausible scenarios for possible action are proposed [15]. Much of the research on arrested senescence is theoretical, and actual experimental efforts to fully stop aging are not likely to occur for some time. The long road to success faced by arrested senescence does not diminish advancements made with decelerated senescence and its potential application to humans. Still, the aspect of research on extreme life extension technologies that focuses on slowing or even halting the aging process is deemed relevant today.
Those technologies are difficult to assess because the means of implementation do not yet exist and are poorly understood. Attitudes towards other kinds of life extension and enhancement are likely also to undergo radical change; the relation between enhancement and meaning of life itself [18]. For example, since around the time immortal transgenic mice were first created, researchers have claimed to have witnessed enhanced lifespans within existent species, something recently accomplished with the augmentation of insulin/IGF-1 signaling in nematodes, mice and later, off-label, humans. This research program could be interpreted both as moderate life-span extension and credible research avenues to subsequent radical lifespan extension.
9.1. Social Implications of Extending Lifespan
Building upon the previous discussions, a much more extensive focus on the social implications of extending human lifespan is offered here. There are many different impacts that would result from efforts to extend human longevity and a variety of different ethical issues and dilemmas that might be generated as a result. Some of these issues may simply stem from the immediate practical implications of a life-extending technology, whereas others are more abstract ramifications of changing human life prospects. The focus in what follows is on the examination of some of these wider social implications.
Expanding human lifespan would have wide-ranging impacts beyond the individual or even closer family spheres. It is expected that these different impacts are generally interrelated, as would be the case with human deaths, and this complicated web of interactions will also determine the actual flow-on impacts of lifespan extension. In discussing what is meant by social context, it is broadly interpreted as not political systems or institutions but how human societies and communities in all of their variety exist and function and how changes to the way in which its member’s lives unfold interactively impact upon the individual, social, economic, cultural and societal facets of human existence. To understand the wider implications of enhancing or extending human longevity, the nature of social context and social interaction needs to be explored.
10. Conclusion and Implications for Society
This final section synthesizes the key findings and insights from the preceding sections. The first section reflects upon the central idea of longevity research, examining its growing importance as lifespans increase and the need to understand aging mechanisms and possible interventions. The methods employed within the field are considered to summarize some of the most notable studies. The next part offers a conclusion regarding longevity research, discussing the current state of knowledge and what is yet to be solved. Finally, the implications for society are reviewed to emphasize the broader societal relevance of this topic.
Human lifespan is increasing, yet the mechanisms behind aging and how to intervene with them remain poorly understood. Longevity research aims to uncover how and why organisms age, as well as investigate the possibility of interventions, through genetic and developmental studies, as well as studies examining pharmaceutical compounds and their effects [14]. Such compounds include rapamycin, resveratrol, rapalogs, metformin, and NAD precursors. Understanding senescent cells, stem cell populations, altered metabolic pathways, and the epigenome’s effect on gene expression is key in longevity research; as is studying a variety of organisms and uniting efforts between geneticists, biologists, chemists, physicists, mathematicians, and medical researchers. Eventually, the hope is to uncover pedestrian interventions to lead to ‘division without cell division’ and have a profound impact on society and the world as a whole.
References:
[1] K. G. Iliadi, D. Knight, and G. L. Boulianne, “Healthy Aging – Insights from Drosophila,” 2012. ncbi.nlm.nih.gov
[2] S. Treaster, D. Karasik, and M. P. Harris, “Footprints in the Sand: Deep Taxonomic Comparisons in Vertebrate Genomics to Unveil the Genetic Programs of Human Longevity,” 2021. ncbi.nlm.nih.gov
[3] C. Caruso, M. Emanuela Ligotti, G. Accardi, A. Aiello et al., “How Important Are Genes to Achieve Longevity?,” 2022. ncbi.nlm.nih.gov
[4] J. Deelen, M. Beekman, M. Capri, C. Franceschi et al., “Identifying the genomic determinants of aging and longevity in human population studies: Progress and challenges,” 2013. ncbi.nlm.nih.gov
[5] D. Rizzuto, N. Orsini, C. Qiu, H. X. Wang et al., “Lifestyle, social factors, and survival after age 75: population based study,” 2012. ncbi.nlm.nih.gov
[6] C. Leitão, A. Mignano, M. Estrela, M. Fardilha et al., “The Effect of Nutrition on Aging—A Systematic Review Focusing on Aging-Related Biomarkers,” 2022. ncbi.nlm.nih.gov
[7] T. Bolin, “Factors that affect human longevity,” 1970. [PDF]
[8] I. Maeve Rea, “Towards ageing well: Use it or lose it: Exercise, epigenetics and cognition,” 2017. ncbi.nlm.nih.gov
[9] D. V. Jeste and A. J. Oswald, “Individual and societal wisdom : explaining the paradox of human aging and high well-being,” 2014. [PDF]
[10] M. Faria, A. Ganz, F. Galkin, A. Zhavoronkov et al., “Psychogenic Aging: A Novel Prospect to Integrate Psychobiological Hallmarks of Aging,” 2024. ncbi.nlm.nih.gov
[11] A. N. Weaver and S. M. Jaeggi, “Activity Engagement and Cognitive Performance Amongst Older Adults,” 2021. ncbi.nlm.nih.gov
[12] Z. Kelly, “Air Pollution and Life Expectancy,” 2017. [PDF]
[13] R. T. Allen, N. M. Hales, A. Baccarelli, M. Jerrett et al., “Countervailing effects of income, air pollution, smoking, and obesity on aging and life expectancy: population-based study of U.S. Counties,” 2016. ncbi.nlm.nih.gov
[14] A. Shinde, G. Deore, K. P. Navsariwala, H. Tabassum et al., “We are all aging, and here’s why,” 2022. ncbi.nlm.nih.gov
[15] E. Ralph, “Longevity Extension from a Socioeconomic Perspective: Plausibility, Misconceptions, and Potential Outcomes,” 2016. [PDF]
[16] P. Balasubramanian, P. R. Howell, and R. M. Anderson, “Aging and Caloric Restriction Research: A Biological Perspective With Translational Potential,” 2017. ncbi.nlm.nih.gov
[17] S. Kumar and T. R. Peterson, “Moonshots for aging,” 2020. ncbi.nlm.nih.gov
[18] P. Garcia-Barranquero, “Old ideas from a new philosophical model: levels and means of human life extension,” 2018. [PDF]