How could that change our understanding about, for starters, chronic disease, aging and obesity?

As millions "age in place," millions more must figure out how to provide their loved ones with increasingly complex care.

Polypharmacy — taking five or more meds at a time — leads to side effects, unnecessary hospitalizations and premature deaths. Researchers and pharmacists are seeking solutions to this serious public health problem that disproportionately affects older adults.

Metabolism is not just about energy—how the body handles nutrient fuel and converts it to useable energetic currency. Metabolism also encompasses synthesis, modification, and exchange of the building blocks for all aspects of cellular function and acts as a sensor and regulator of cellular activities, in which individual moieties within metabolic pathways influence cellular responses. A substantial amount of the energy taken in each day is required to simply sustain life; the energetic demands of physical activity are superimposed on a vastly integrated machinery. Metabolic status has been linked to innumerable diseases and disorders, including those most prevalent with age ([ 1 ][1]–[ 3 ][2]). On page 808 of this issue, Pontzer et al. ([ 4 ][3]) analyze energy expenditure in more than 6400 males and females from 29 countries across the globe, aged between 8 days and 95 years, and show distinct metabolic phases during development and aging. An understanding of energy expenditure across the life span must grapple with the diversity of humans, including sex, race, body composition, and their environment. Estimates of energy expenditure can be captured with indirect calorimetry that measures gas exchange and heat production of sequestered individuals, or by the doubly labeled water (DLW) method in free living individuals. The DLW technique is based on the relative bodily elimination rates of isotopes of oxygen and hydrogen ([ 5 ][4]). In the time since methods were developed for application in humans ([ 6 ][5]), the use of DLW has been steadily growing. Associated costs of isotope dosing have limited most studies to relatively small cohorts, but there has been commitment among the research community to share data and to develop integrative methods so that large-cohort data analysis might be undertaken ([ 7 ][6]). In the study of Pontzer et al. , energy expenditure was adjusted to fat-free mass to account for differences in body size, revealing intrinsic shifts in metabolic status over the course of development, maturation, and aging. The authors identify inflection points that are the boundaries for four distinct phases. It seems clear from their data that infants and adolescents form two different metabolic categories. It has been said before, but children are not just small adults ([ 8 ][7]). That young people represent separate metabolic status categories has important implications for recommendations about diet and physical activity, not to mention pharmaceutical dose recommendations for younger persons. The remaining two phases cover adulthood and advanced age. Adjusted energy expenditure is notably stable from 20 years of age up to about 60 years of age, at which point a gradual decline is observed (see the figure). The decline from age 60 is thought to reflect a change in tissue-specific metabolism, the energy expended on maintenance. It cannot be a coincidence that the increase in incidence of noncommunicable diseases and disorders begins in this same time frame ([ 9 ][8]). These findings indicate that life stage needs to be carefully considered when choosing disease models. This is particularly important for research on the etiology of age-associated diseases and disorders ([ 10 ][9]). Pathways and factors that are readily targetable in young growing animals may not be as sensitive or even responsive in older animals, and young models fail to capture the aged environment and may miss interactions that emerge as a result of intrinsic differences in metabolic status. ![Figure][10] Life span of metabolism Measures of energy expenditure (adjusted for fat-free mass) identify three inflection points over the human life span. Energy expenditure increases during infancy and childhood and then declines through adolescence, a plateau phase lasts throughout adulthood, and a second declining phase occurs from 60 years of age. The marked rise in incidence of chronic disease from late middle age aligns with the shift in energy expenditure and loss of adiposity, suggesting that metabolism may be a driver in aging biology. GRAPHIC: A. MASTIN/ SCIENCE The impact of body size on metabolic rate has been discussed and explored for decades ([ 11 ][11]). Total energy expenditure is sex dimorphic, with lower levels in females than in males; however, accounting for fat-free mass removes this distinction. It is important that contributions from physical activity and tissue-specific metabolic rates, both of which change over the human life span, must be accounted for if computational models are to fit the observed data. Although not the focus of the work, Pontzer et al. identified substantial heterogeneity in body composition among individuals. Challenges arising from heterogeneity among individuals are reflected in the growing enthusiasm for precision medicine ([ 12 ][12]). It is abundantly clear that one size does not fit all. By adjusting for fat-free mass, this study peels some of this variance away to reveal intrinsic shifts in metabolism that are matched to life phase. There is considerable heterogeneity in how and when aging manifests in terms of disease incidence ([ 13 ][13]). It would be interesting to explore how mid-life disposition informs outcomes in advanced age and how well disease burden among individuals links to age-associated changes in their tissue-specific metabolism. The causal factors in age-related vulnerability to disease no doubt reside in the documented changes in cellular biology, tissue physiology, and systemic homeostasis. Studies of laboratory animals have honed in on metabolism as a central theme in aging and in delayed aging through caloric restriction ([ 14 ][14]). Differences in metabolism are predicted to affect derivation of energy from nutrient sources, foundational material for synthesis of cellular machinery and communication relays, and the ability to optimize cellular activities according to prevailing conditions, whether external or internal. It will come as no surprise then that recent efforts to identify pharmacological agents that positively affect health in aging converge on metabolism ([ 15 ][15]). The Pontzer et al. study provides important new insights into human metabolism; the unprecedented scale and scope of the study is matched by the outstanding collaborative spirit that made it possible. 1. [↵][16]1. N. N. Pavlova, 2. C. B. Thompson , Cell Metab. 23, 27 (2016). [OpenUrl][17][CrossRef][18][PubMed][19] 2. 1. S. Costantino, 2. F. Paneni, 3. F. Cosentino , J. Physiol. 594, 2061 (2016). [OpenUrl][20] 3. [↵][21]1. S. Camandola, 2. M. P. Mattson , EMBO J. 36, 1474 (2017). [OpenUrl][22][Abstract/FREE Full Text][23] 4. [↵][24]1. H. Pontzer et al ., Science 373, 808 (2021). [OpenUrl][25][Abstract/FREE Full Text][26] 5. [↵][27]1. J. R. Speakman , Am. J. Clin. Nutr. 68, 932S (1998). [OpenUrl][28][Abstract][29] 6. [↵][30]1. D. A. Schoeller , J. Nutr. 118, 1278 (1988). [OpenUrl][31][Abstract/FREE Full Text][32] 7. [↵][33]1. J. R. Speakman et al ., Cell Rep. Med. 2, 100203 (2021). [OpenUrl][34][CrossRef][35][PubMed][36] 8. [↵][37]1. P. F. Saint-Maurice, 2. Y. Kim, 3. G. J. Welk, 4. G. A. Gaesser , Eur. J. Appl. Physiol. 116, 29 (2016). [OpenUrl][38] 9. [↵][39]NCD Countdown collaborators, Lancet 392, 1072 (2018). [OpenUrl][40][CrossRef][41][PubMed][42] 10. [↵][43]1. B. K. Kennedy et al ., Cell 159, 709 (2014). [OpenUrl][44][CrossRef][45][PubMed][46] 11. [↵][47]1. M. Kleiber , Physiol. Rev. 27, 511 (1947). [OpenUrl][48][CrossRef][49][PubMed][50][Web of Science][51] 12. [↵][52]1. M. A. Haendel, 2. C. G. Chute, 3. P. N. Robinson , N. Engl. J. Med. 379, 1452 (2018). [OpenUrl][53] 13. [↵][54]1. D. J. Lowsky, 2. S. J. Olshansky, 3. J. Bhattacharya, 4. D. P. Goldman , J. Gerontol. A Biol. Sci. Med. Sci. 69, 640 (2014). [OpenUrl][55][CrossRef][56][PubMed][57][Web of Science][58] 14. [↵][59]1. P. Balasubramanian, 2. P. R. Howell, 3. R. M. Anderson , EBioMedicine 21, 37 (2017). [OpenUrl][60] 15. [↵][61]1. L. Partridge, 2. M. Fuentealba, 3. B. K. Kennedy , Nat. Rev. Drug Discov. 19, 513 (2020). [OpenUrl][62][CrossRef][63] Acknowledgments: T.W.R. and R.M.A. are supported by NIH/NIA grants AG040178, AG057408, and AG067330; the Department for Veterans Affairs BX003846; and the Simons Foundation. 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Volume 44 (2021) - Article 52 | Pages 1271–1294

An economic analysis suggests that targeting aging offers potentially larger economic gains than eradicating individual diseases. Slowing aging to increase life expectancy by 1 year is worth US$38 trillion, and by 10 years, US$367 trillion.

Listen to this episode from Psychologists Off the Clock on Spotify. In 2020, the global market for anti-aging products was estimated at US$52.5 Billion and is projected to reach US$83.2 Billion by 2027. Some of this market is certainly due to ageism, pseudoscience, and harmful marketing practices. However, ideas around aging (and the way it’s portrayed in media and marketing) seem to be changing for the better, and some anti-aging techniques are showing great promise. Dr. Andrew Steele, author of Ageless, has dedicated his professional career to identifying factors that age us. In this episode of Psychologists Off the Clock, he and Diana discuss the science behind why we grow old and the evidence-based approaches individuals of all ages can use to target those aging factors. Join us in this episode to learn basic strategies you can implement to inhibit the aging process and enhance your quality of life today! Listen and Learn: Diana and Debbie’s thoughts on the pseudoscience and fear that typically fosters ageism and the evidence-based approaches to healthy agingAndrew’s expert description of the humanitarian science of aging (and why it’s so important we study this right now!)Ten key factors that contribute to aging and evidence-based ways to target themWhat evolutionary neglect is and why we have evolved to grow oldAndrew’s expert explanation of senescent cells and practical advice for targeting them Basic strategies you can implement today to inhibit the aging process and enhance your quality of lifeNew and incoming interventions designed to increase telomere lengthThe psychological impacts of living longer The values underlying Andrew’s mission of building respectful, supportive communities for the elderlyEasy anti-aging practices young people can implement into their daily routine Resources: Andrew’s book, Ageless: The New Science of Getting Older Without Getting Old Elizabeth Blackburn and Elissa Epel’s book, The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer Attend Debbie’s webinar on ACT for Burnout!Grab your copy of all our favorite books at bookshop.org/shop/offtheclockpsych.Check out Debbie, Diana, Yael, and Jill’s websites to access their offerings, sign up for their newsletters, buy their books, and more!  Dr. Andrew Steele About Andrew Steele: After obtaining a PhD in physics from the University of Oxford, Dr. Andrew Steele decided that ageing was the most important scientific challenge of our time, and switched fields to computational biology. He worked at the Francis Crick Institute, using machine learning to decode our DNA and predict heart attacks using patients' medical records. He is now a full-time science writer and presenter based in London. He has appeared on Discovery and the BBC. Follow him on instagram @andrewjsteele, twitter @statto, and facebook @DrAndrewSteele.  Read his Psychology Today interview, and check out his Today Show appearance Related Episodes: Episode 125. Why We Age and the Science of Longevity with David SinclairEpisode 13. Healthy Aging and the Brain Episode 194. How to Be (and raise) an Adult with Julie Lythcott-HaimsEpisode 174. How to Work and Parent Mindfully with Lori Mihalich-Levin

The Society Pages (TSP) is an open-access social science project headquartered in the Department of Sociology at the University of Minnesota

Recently researchers proposed the term ‘Type-3-Diabetes’ for Alzheimer's disease (ad) because of the shared molecular and cellular features among Type…

And what else you need to know today.

Prioritizing health of the world’s population would add 10 healthy years in midlife and $12 trillion to the global economy .