Taurine deficiency as a driver of aging

Singh, Parminder; Gollapalli, Kishore; Mangiola, Stefano; Schranner, Daniela; Yusuf, Mohd Aslam; Chamoli, Manish; Shi, Sting L.; Lopes Bastos, Bruno; Nair, Tripti; Riermeier, Annett; Vayndorf, Elena M.; Wu, Judy Z.; Nilakhe, Aishwarya; Nguyen, Christina Q.; Muir, Michael; Kiflezghi, Michael G.; Foulger, Anna; Junker, Alex; Devine, Jack; Sharan, Kunal; Chinta, Shankar J.; Rajput, Swati; Rane, Anand; Baumert, Philipp; Schönfelder, Martin; Iavarone, Francescopaolo; di Lorenzo, Giorgia; Kumari, Swati; Gupta, Alka; Sarkar, Rajesh; Khyriem, Costerwell; Chawla, Amanpreet S.; Sharma, Ankur; Sarper, Nazan; Chattopadhyay, Naibedya; Biswal, Bichitra K.; Settembre, Carmine; Nagarajan, Perumal; Targoff, Kimara L.; Picard, Martin; Gupta, Sarika; Velagapudi, Vidya; Papenfuss, Anthony T.; Kaya, Alaattin; Ferreira, Miguel Godinho; Kennedy, Brian K.; Andersen, Julie K.; Lithgow, Gordon J.; Ali, Abdullah Mahmood; Mukhopadhyay, Arnab; Palotie, Aarno; Kastenmüller, Gabi; Kaeberlein, Matt; Wackerhage, Henning; Pal, Bhupinder; Yadav, Vijay K.     «

Singh, Parminder; Gollapalli, Kishore; Mangiola, Stefano; Schranner, Daniela; Yusuf, Mohd Aslam; Chamoli, Manish; Shi, Sting L.; Lopes Bastos, Bruno; Nair, Tripti; Riermeier, Annett; Vayndorf, Elena M.; Wu, Judy Z.; Nilakhe, Aishwarya; Nguyen, Christina Q.; Muir, Michael; Kiflezghi, Michael G.; Foulger, Anna; Junker, Alex; Devine, Jack; Sharan, Kunal; Chinta, Shankar J.; Rajput, Swati; Rane, Anand; Baumert, Philipp; Schönfelder, Martin; Iavarone, Francescopaolo; di Lorenzo, Giorgia; Kumari, Swat...     »

Aging is an inevitable multifactorial process. Aging-related changes manifest as the “hallmarks of aging,” cause organ functions to decline, and increase the risk of disease and death. Aging is associated with systemic changes in the concentrations of molecules such as metabolites. However, whether such changes are merely the consequence of aging or whether these molecules are drivers of aging remains largely unexplored. If these were blood-based drivers of aging, then restoring their concentration or functions to “youthful” levels could serve as an antiaging intervention. Taurine, a semiessential micronutrient, is one of the most abundant amino acids in humans and other eukaryotes. Earlier studies have shown that the concentration of taurine in blood correlates with health, but it is unknown whether blood taurine concentrations affect aging. To address this gap in knowledge, we measured the blood concentration of taurine during aging and investigated the effect of taurine supplementation on health span and life span in several species. Blood concentration of taurine declines with age in mice, monkeys, and humans. To investigate whether this decline contributes to aging, we orally fed taurine or a control solution once daily to middle-aged wild-type female and male C57Bl/6J mice until the end of life. Taurine-fed mice of both sexes survived longer than the control mice. The median life span of taurine-treated mice increased by 10 to 12%, and life expectancy at 28 months increased by about 18 to 25%. A meaningful antiaging therapy should not only improve life span but also health span, the period of healthy living. We, therefore, investigated the health of taurine-fed middle-aged mice and found an improved functioning of bone, muscle, pancreas, brain, fat, gut, and immune system, indicating an overall increase in health span. We observed similar effects in monkeys. To check whether the observed effects of taurine transcended the species boundary, we investigated whether taurine supplementation increased life span in worms and yeast. Although taurine did not affect the replicative life span of unicellular yeast, it increased life span in multicellular worms. Investigations into the mechanism or mechanisms through which taurine supplementation improved the health span and life span revealed that taurine positively affected several hallmarks of aging. Taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammation. An association analysis of metabolite clinical risk factors in humans showed that lower taurine, hypotaurine, and N-acetyltaurine concentrations were associated with adverse health, such as increased abdominal obesity, hypertension, inflammation, and prevalence of type 2 diabetes. Moreover, we found that a bout of exercise increased the concentrations of taurine metabolites in blood, which might partially underlie the antiaging effects of exercise. Taurine abundance decreases during aging. A reversal of this decline through taurine supplementation increases health span and life span in mice and worms and health span in monkeys. This identifies taurine deficiency as a driver of aging in these species. To test whether taurine deficiency is a driver of aging in humans as well, long-term, well-controlled taurine supplementation trials that measure health span and life span as outcomes are required.      «

Aging is an inevitable multifactorial process. Aging-related changes manifest as the “hallmarks of aging,” cause organ functions to decline, and increase the risk of disease and death. Aging is associated with systemic changes in the concentrations of molecules such as metabolites. However, whether such changes are merely the consequence of aging or whether these molecules are drivers of aging remains largely unexplored. If these were blood-based drivers of aging, then restoring their concentrat...     »